Molecular Profile Detail

Profile Name KIT over exp
Gene Variant Detail

KIT over exp (no effect)

Relevant Treatment Approaches

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
KIT D816F Advanced Solid Tumor resistant Imatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT D816F were resistant to Gleevec (imatinib mesylate) in culture (PMID: 16397263). 16397263
KIT D816V KIT V560G mast-cell leukemia sensitive Dasatinib Preclinical Actionable In a preclinical study, Sprycel (dasatinib) inhibited growth and induced apoptosis in a mast-cell leukemia cell line harboring both KIT V560G and KIT D816V in culture (PMID: 18024392). 18024392
KIT D816V KIT V560G mast-cell leukemia sensitive Ponatinib Preclinical Actionable In a preclinical study, Iclusig (ponatinib) inhibited growth of a human mast cell line harboring both KIT V560G and KIT D816V in culture (PMID: 24552773). 24552773
KIT D816V KIT V560G mast-cell leukemia sensitive Avapritinib Preclinical - Cell culture Actionable In a preclinical study, BLU-285 inhibited Kit phosphorylation and proliferation of a mast cell leukemia cell line harboring KIT D816V and V560G in culture (PMID: 29093181). 29093181
KIT D816V KIT V560G mast-cell leukemia sensitive BPR1J373 Preclinical - Cell culture Actionable In a preclinical study, a mast-cell leukemia cell line simultaneously harboring KIT D816V and KIT V560G was sensitive to BPR1J373 in culture, demonstrating inhibition of Kit phosphorylation and apoptotic activity (PMID: 27512117). 27512117
KIT D816V KIT V560G mast cell neoplasm resistant Quizartinib Preclinical Actionable In a preclinical study, KIT D816V conferred resistance to Quizartinib in a mast cell line harboring both KIT V560G and KIT D816V in culture (PMID: 23497317). 23497317
KIT D816V NRAS Q61R melanoma no benefit Pembrolizumab + Trametinib Case Reports/Case Series Actionable In a clinical case study, a melanoma patient harboring KIT D816V and NRAS Q61R demonstrated progressive disease when treated with a combination of Mekinist (trametinib) and Keytruda (pembrolizumab) (PMID: 28514312). 28514312
KIT D816V hematologic cancer resistant Imatinib Preclinical Actionable In a preclinical study, a mouse myeloid cell line expressing KIT D816V demonstrated resistance to Gleevec (imatinib) in culture (PMID: 12481435). 12481435
KIT D816V Advanced Solid Tumor resistant Sunitinib Preclinical Actionable In a preclinical study, KIT D816V mutations demonstrated resistance to Sutent (sunitinib) in a biochemical assay (PMID: 19164557). 19164557
KIT D816V Advanced Solid Tumor resistant Sunitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT D816V were resistant to treatment with Sutent (sunitinib) in culture (PMID: 24205792). 24205792
KIT D816V Advanced Solid Tumor resistant Quizartinib Preclinical Actionable In a preclinical study, transformed cells expressing KIT D816V demonstrated resistance to Quizartinib in culture (PMID: 23497317). 23497317
KIT D816V Advanced Solid Tumor resistant Imatinib Preclinical Actionable In a preclinical study, transformed cells expressing KIT D816V demonstrated resistance to Gleevec (imatinib mesylate) in culture (PMID: 15790786). 15790786
KIT D816V mast cell neoplasm predicted - sensitive Avapritinib Phase I Actionable In a Phase I trial, patients with either aggressive systemic mastocytosis, mast cell leukemia, or systemic mastocytosis with an associated hematologic neoplasm harboring KIT D816V demonstrated a reduction in mast cell burden and a decrease in KIT D816V allelic fraction when treated with BLU-285 (ASH Annual Meeting, Dec 2017, Plenary 2). detail...
KIT D816V Indication other than cancer resistant Imatinib FDA contraindicated Actionable Gleevec (imatinib) is not indicated for patients with aggressive systemic mastocytosis harboring KIT D816V (FDA.gov). detail... detail...
KIT D816V Advanced Solid Tumor decreased response Nilotinib Preclinical Actionable In a preclinical study, Tasigna (nilotinib) decreased viability of cells expressing KIT D816V in culture, but did not inhibit KIT phosphorylation or growth of KIT D816V-expressing tumors in mouse models (PMID: 20442311). 20442311
KIT D816V hematologic cancer resistant Sorafenib Preclinical Actionable In a preclinical study, transformed hematopoietic cells expressing KIT D816V demonstrated resistance to Nexavar (sorafenib) in culture (PMID: 17229632). 17229632
KIT D816V acute myeloid leukemia sensitive Cytarabine + Dasatinib Case Reports/Case Series Actionable In a clinical case study, a patient with acute myeloid leukemia harboring KIT D816V achieved long-term remission and loss of KIT D816V following treatment with the combination of Sprycel (dasatinib) and Cytosar-U (cytarabine) (PMID: 18986703). 18986703
KIT D816V hematologic cancer sensitive FF-10101 Preclinical - Cell culture Actionable In a preclinical study, FF-10101, as compared to Quizartinib, inhibited cell proliferation of transformed 32Dcl3 murine myeloid cells expressing human Kit D816V (PMID: 29187377). 29187377
KIT D816V Advanced Solid Tumor resistant Cabozantinib Preclinical Actionable In a preclinical study, transformed cells expressing KIT D816V demonstrated resistance to Cometriq (cabozantinib) in culture (PMID: 24205792). 24205792
KIT D816V Advanced Solid Tumor resistant Flumatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT D816V were resistant to treatment with Flumatinib in culture (PMID: 24205792). 24205792
KIT D816V Advanced Solid Tumor predicted - sensitive BPR1J373 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT D816V were sensitive to BPR1J373, demonstrating inhibition of Kit phosphorylation (PMID: 27512117). 27512117
KIT D816V Advanced Solid Tumor resistant Ponatinib Preclinical Actionable In a preclinical study, Iclusig (ponatinib) did not inhibit growth of transformed cells expressing KIT D816V in culture (PMID: 22301675). 22301675
KIT V559D KIT V654A Advanced Solid Tumor sensitive Sunitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing KIT V559D and KIT V654A were sensitive to treatment with Sutent (sunitinib) in culture, demonstrating decreased cell proliferation (PMID: 24205792). 24205792
KIT V559D KIT V654A Advanced Solid Tumor sensitive Sunitinib Preclinical - Cell culture Actionable In a preclinical study, Sutent (sunitinib) inhibited proliferation of transformed cells expressing KIT V654A and KIT V559D in culture (PMID: 31205508). 31205508
KIT V559D KIT V654A Advanced Solid Tumor sensitive Axitinib Preclinical - Cell culture Actionable In a preclinical study, Inlyta (axitinib) inhibited KIT phosphorylation and proliferation of transformed cells expressing KIT V654A and KIT V559D in culture (PMID: 31205508). 31205508
KIT W557_K558del KIT V654A Advanced Solid Tumor sensitive Sunitinib Preclinical - Cell line xenograft Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT V654A demonstrated sensitivity to treatment with Sutent (sunitinib) in both culture and cell line xenograft models, resulting in reduced cell viability, decreased tumor volume, and tumor regression (PMID: 25239608). 25239608
KIT W557_K558del KIT V654A gastrointestinal stromal tumor sensitive Avapritinib Preclinical - Pdx Actionable In a preclinical study, BLU-285 inhibited Kit phosphorylation and resulted in tumor regression in patient-derived xenograft models of Gleevec (imatinib)-resistant gastrointestinal stromal tumor harboring KIT W557_K558del and V654A (PMID: 29093181). 29093181
KIT W557_K558del KIT V654A Advanced Solid Tumor resistant Regorafenib Preclinical Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT V654A demonstrated resistance to treatment with Stivarga (regorafenib) in culture (PMID: 25239608). 25239608
KIT W557_K558del KIT V654A Advanced Solid Tumor sensitive Ponatinib Preclinical - Cell line xenograft Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT V654A demonstrated sensitivity to treatment with Iclusig (ponatinib) in both culture and cell line xenograft models, resulting in reduced cell viability and decreased tumor volume (PMID: 25239608). 25239608
KIT W557_K558del KIT V654A Advanced Solid Tumor no benefit Imatinib Preclinical - Cell line xenograft Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT V654A demonstrated no response to treatment with Gleevec (imatinib) in both culture and xenograft models (PMID: 25239608). 25239608
KIT V560D KIT V654A Advanced Solid Tumor sensitive Motesanib Preclinical - Cell culture Actionable In a preclinical study, Motesanib (AMG 706) inhibited KIT phosphorylation and growth of cells expressing a KIT V560D/V654A double mutation in culture (PMID: 20633291). 20633291
KIT V560D KIT V654A Advanced Solid Tumor resistant Flumatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing KIT V560D and KIT V654A were resistant to Flumatinib in culture (PMID: 24205792). 24205792
KIT V560_L576del KIT V654A gastrointestinal stromal tumor sensitive Sunitinib Preclinical Actionable In a preclinical study, a patient derived GIST cell line co-harboring KIT V560_L576del and KIT V654A demonstrated sensitivity to treatment with Sutent (sunitinib) (PMID: 25239608). 25239608
KIT exon 11 KIT V654A gastrointestinal stromal tumor sensitive Imatinib + MK2206 Preclinical - Cell culture Actionable In a preclinical study, the combination of Gleevec (imatinib) and MK2206 demonstrated synergy in inhibiting growth of a Gleevec (imatinib)-resistant gastrointestinal stromal tumor cell line harboring a KIT exon 11 deletion mutation and KIT V654A in culture (PMID: 27370604). 27370604
KIT V560del KIT V654A Advanced Solid Tumor sensitive Nilotinib Preclinical - Cell culture Actionable In a preclinical study, Tasigna (nilotinib) inhibited proliferation of transformed cells expressing a KIT V560del/V654A double mutation in culture (PMID: 17699867). 17699867
KIT K558_V560del KIT V654A gastrointestinal stromal tumor predicted - resistant Imatinib Case Reports/Case Series Actionable In a clinical study, KIT V654A was identified as a secondary mutation in a patient with gastrointestinal stromal tumor harboring a primary KIT K558_V560del mutation, who developed resistance to Gleevec (imatinib) (PMID: 18488160). 18488160
KIT V654A Advanced Solid Tumor sensitive Axitinib Preclinical - Cell line xenograft Actionable In a preclinical study, Inlyta (axitinib) inhibited KIT phosphorylation and proliferation of transformed cells expressing KIT V654A in culture, and inhibited tumor growth in xenograft models (PMID: 31205508). 31205508
KIT V654A Advanced Solid Tumor resistant Imatinib Preclinical Actionable In a preclinical study, cells expressing KIT V654A demonstrated resistance to Gleevec (imatinib) in culture (PMID: 16751810). 16751810
KIT V654A Advanced Solid Tumor sensitive Sunitinib Preclinical - Cell culture Actionable In a preclinical study, Sutent (sunitinib) inhibited proliferation of transformed cells expressing KIT V654A in culture (PMID: 31205508). 31205508
KIT V654A Advanced Solid Tumor sensitive Ponatinib Preclinical Actionable In a preclinical study, cells expressing KIT V654A demonstrated some sensitivity to Iclusig (ponatinib) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT V654A gastrointestinal stromal tumor predicted - sensitive AZD3229 Preclinical - Pdx Actionable In a preclinical study, AZD3229 inhibited Kit signaling, resulted in tumor regression in patient-derived xenograft (PDX) models of gastrointestinal stromal tumor harboring KIT V654A (Proceedings of the American Association for Cancer Research, Vol 60, Mar 2019, Abstract #1328). detail...
KIT V569_L576del KIT V654A KIT N822K gastrointestinal stromal tumor predicted - resistant Imatinib Case Reports/Case Series Actionable In a clinical study, KIT V654A and KIT N822K were identified as secondary mutations in a patient with gastrointestinal stromal tumor harboring a primary KIT V569_L576del mutation, who developed resistance to Gleevec (imatinib) (PMID: 18488160). 18488160
KIT D820V gastrointestinal stromal tumor sensitive Avapritinib Phase I Actionable In a Phase I trial, BLU-285 treatment resulted in tumor reduction lasting through 15 cycles of treatment in a patient with gastrointestinal stromal tumor harboring KIT D820V, whose disease had progressed on previous Gleevec (imatinib), Sutent (sunitinib), and Stivarga (regorafenib) treatment (PMID: 29093181; NCT02508532). 29093181
KIT W557_K558del KIT D816E KIT D820V gastrointestinal stromal tumor predicted - resistant Imatinib Case Reports/Case Series Actionable In a clinical study, KIT D816E and D820V were identified as secondary mutations in a patient with gastrointestinal stromal tumor harboring KIT W557_K558del who developed resistance to Gleevec (imatinib) (PMID: 18294292). 18294292
KIT V560del KIT over exp thymic carcinoma predicted - sensitive Imatinib Case Reports/Case Series Actionable In a clinical case report, a patient with metastatic thymic carcinoma harboring KIT V560del with KIT over expression initially demonstrated stable disease and reduction in metastatic lesions following treatment with Gleevec (imatinib), but progressed after 6 months (PMID: 15201427). 15201427
KIT V560del Advanced Solid Tumor sensitive Sunitinib Preclinical Actionable In a preclinical study, Sutent (sunitinib) inhibited growth of transformed cell lines over expressing KIT V560del in culture (PMID: 19861435). 19861435
KIT V560del Advanced Solid Tumor sensitive Imatinib Preclinical Actionable In a preclinical study, Gleevec (imatinib) inhibited growth of transformed cell lines over expressing KIT V560del in culture (PMID: 19861435). 19861435
KIT L576P KIT W557R melanoma sensitive Nilotinib Phase II Actionable In a Phase II trial, Tasigna (nilotinib) resulted in an overall response rate of 26.2% (11/41) including a melanoma patient co-harboring KIT L576P and KIT W557R demonstrating a partial response and a progression free survival of 5.3 months and overall survival of 14.7 months when treated with Tasigna (nilotinib) (PMID: 28327988). 28327988
KIT W557R melanoma sensitive Nilotinib Phase II Actionable In a Phase II trial, Tasigna (nilotinib) resulted in an overall response rate of 26.2% (11/41) including a melanoma patient harboring KIT W557R demonstrating a partial response and progression free survival of 35.4 months and overall survival of 35.4 months (PMID: 28327988). 28327988
KIT L576P melanoma sensitive Nilotinib Phase II Actionable In a Phase II trial, Tasigna (nilotinib) resulted in an overall response rate of 26.2% (11/41) including three melanoma patients harboring KIT L576P demonstrating a partial response (PMID: 28327988). 28327988
KIT L576P melanoma sensitive SEL201 Preclinical - Cell line xenograft Actionable In a preclinical study, SEL201 inhibited MNK pathway signaling and growth of melanoma cells harboring KIT L576P in culture, and suppressed tumor metastasis in xenograft models (PMID: 29035277). 29035277
KIT L576P Advanced Solid Tumor sensitive Axitinib Preclinical - Cell culture Actionable In a preclinical study, Inlyta (axitinib) inhibited KIT phosphorylation and proliferation of transformed cells expressing KIT L576P in culture (PMID: 31205508). 31205508
KIT L576P melanoma sensitive Dasatinib Case Reports/Case Series Actionable In a clinical study, two patients with melanoma harboring KIT L576P, one who had progressed on Gleevec (imatinib), demonstrated initial clinical benefit following treatment with Sprycel (dasatinib); however, one patient progressed after 3 months, and the other patient progressed after 4 months of treatment (PMID: 19671763). 19671763
KIT L576P melanoma sensitive Dasatinib Preclinical - Cell culture Actionable In a preclinical study, Sprycel (dasatinib) inhibited MNK pathway activation and proliferation of melanoma cell lines harboring KIT L576P in culture (PMID: 29035277). 29035277
KIT L576P melanoma unknown Imatinib Case Reports/Case Series Actionable In a clinical case study, Gleevec (imatinib) treatment resulted in initial tumor reduction, but was followed by disease progression at all tumor sites in a patient with metastasized labial melanoma harboring KIT L576P (PMID: 20372153). 20372153
KIT L576P melanoma predicted - sensitive Bevacizumab + Sorafenib Case Reports/Case Series Actionable In a Phase I trial, a melanoma patient harboring KIT L576P demonstrated sensitivity to the combination treatment of Nexavar (sorafenib) and Avastin (bevacizumab), resulting in a partial response for 8 months (PMID: 25363205). 25363205
KIT act mut gastrointestinal stromal tumor sensitive Cabozantinib Preclinical Actionable In a preclinical study, Cometriq (cabozantinib) decreased cell viability in imatinib-sensitive and resistant gastrointestinal stromal tumor (GIST) cell lines harboring KIT activating mutations in culture, and induced tumor regression in KIT-mutant GIST mouse models (PMID: 25836719). 25836719
KIT act mut gastrointestinal stromal tumor sensitive Pexidartinib Preclinical - Cell line xenograft Actionable In a preclinical study, PLX3397 inhibited growth of gastrointestinal stromal tumor cell lines harboring KIT activating mutations in culture and in cell line xenograft models (PMID: 24583793). 24583793
KIT act mut melanoma sensitive Imatinib Guideline Actionable Gleevec (imatinib) is included in guidelines as second-line therapy for metastatic or unresectable melanoma patients with KIT activating mutations (NCCN.org). detail...
KIT act mut gastrointestinal stromal tumor not applicable N/A Guideline Diagnostic KIT activating mutations aid the diagnosis of gastrointestinal stromal tumor (NCCN.org). detail...
KIT act mut Advanced Solid Tumor sensitive PLX9486 Preclinical Actionable In a preclinical study, PLX9486 inhibited KIT mutations, including exon 17 mutations, and demonstrated in vivo and in vitro activity against tumors harboring KIT exon 17 mutations (Cancer Res February 1, 2016 76; IA32). detail...
KIT Y553N thymic carcinoma sensitive Imatinib Case Reports/Case Series Actionable In a clinical case study, a patient with metastatic thymic carcinoma harboring KIT Y553N demonstrated improved clinical performance and reduction in metastatic lesions following treatment with Gleevec (imatinib) (PMID: 21969494). 21969494
KIT P551_V555delinsTL gastrointestinal stromal tumor sensitive Sorafenib Preclinical - Pdx Actionable In a preclinical study, Nexavar (sorafenib) inhibited Erk signaling, induced apoptosis, resulted in tumor growth inhibition in patient derived xenograft models of gastrointestinal stromal tumor harboring KIT P551_V555delinsTL (PMID: 19139124). 19139124
KIT N822K KIT V559D Advanced Solid Tumor sensitive Flumatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing KIT N822K and KIT V559D were sensitive to Flumatinib in culture, demonstrating decreased cell proliferation and inhibition of Kit, Erk 1/2, and Stat3 phosphorylation (PMID: 24205792). 24205792
KIT N822K KIT V559D Advanced Solid Tumor no benefit Sunitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing KIT N822K and KIT V559D were insensitive to Sutent (sunitinib) in culture (PMID: 24205792). 24205792
KIT D820Y KIT V559D Advanced Solid Tumor sensitive Sorafenib Preclinical - Cell culture Actionable In a preclinical study, Nexavar (sorafenib) inhibited proliferation of transformed cells expressing a KIT V559D/D820Y double mutation in culture (PMID: 17699867). 17699867
KIT D820Y KIT V559D Advanced Solid Tumor sensitive Dasatinib Preclinical - Cell culture Actionable In a preclinical study, Sprycel (dasatinib) inhibited proliferation of transformed cells expressing a KIT V559D/D820Y double mutation in culture (PMID: 17699867). 17699867
KIT D820Y KIT V559D Advanced Solid Tumor sensitive Nilotinib Preclinical - Cell culture Actionable In a preclinical study, Tasigna (nilotinib) inhibited proliferation of transformed cells expressing a KIT V559D/D820Y double mutation in culture, with increased potency compared to Sprycel (dasatinib) or Nexavar (sorafenib) (PMID: 17699867). 17699867
KIT A829P KIT V559D Advanced Solid Tumor no benefit Sunitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing KIT A829P and KIT V559D were insensitive to Sutent (sunitinib) in culture (PMID: 24205792). 24205792
KIT A829P KIT V559D Advanced Solid Tumor sensitive Flumatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing KIT A829P and KIT V559D were sensitive to Flumatinib in culture, demonstrating decreased cell proliferation and inhibition of Kit, Erk1/2, and Stat3 phosphorylation (PMID: 24205792). 24205792
KIT T670I KIT V559D Advanced Solid Tumor sensitive Sunitinib Preclinical - Cell culture Actionable In a preclinical study, Sutent (sunitinib) inhibited proliferation of transformed cells expressing KIT T670I and KIT V559D in culture (PMID: 31205508). 31205508
KIT T670I KIT V559D Advanced Solid Tumor sensitive Sunitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing KIT V559D and KIT T670I were sensitive to treatment with Sutent (sunitinib) in culture, demonstrating decreased cell proliferation (PMID: 24205792). 24205792
KIT V559D Advanced Solid Tumor sensitive Sunitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT V559D were sensitive to Sutent (sunitinib), demonstrating decreased cell proliferation in culture and inhibition of Kit, Erk1/2, and Stat3 phosphorylation (PMID: 24205792). 24205792
KIT V559D Advanced Solid Tumor sensitive Ponatinib Preclinical Actionable In a preclinical study, cells expressing KIT V559D demonstrated sensitivity to Iclusig (ponatinib) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT V559D Advanced Solid Tumor sensitive Axitinib Preclinical - Cell culture Actionable In a preclinical study, Inlyta (axitinib) inhibited KIT phosphorylation and proliferation of transformed cells expressing KIT V559D in culture (PMID: 31205508). 31205508
KIT V559D melanoma sensitive Nilotinib Phase II Actionable In a Phase II trial, Tasigna (nilotinib) resulted in an overall response rate of 26.2% (11/41) including a melanoma patient harboring KIT V559D demonstrating a partial response and progression free survival of 28.3 months and overall survival of 28.3 months (PMID: 28327988). 28327988
KIT V559D Advanced Solid Tumor sensitive Flumatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT V559D were sensitive to Flumatinib, demonstrating decreased cell proliferation in culture and inhibition of Kit, Erk1/2, and Stat3 phosphorylation (PMID: 24205792). 24205792
KIT V559D gastrointestinal stromal tumor sensitive Axitinib Preclinical - Patient cell culture Actionable In a preclinical study, Inlyta (axitinib) inhibited proliferation of gastrointestinal stromal tumor patient-derived primary cells harboring KIT V559D in culture (PMID: 31205508). 31205508
KIT V559D Advanced Solid Tumor sensitive Dasatinib Preclinical - Cell culture Actionable In a preclinical study, Sprycel (dasatinib) decreased KIT signaling, and inhibited growth and induced apoptosis of transformed cells expressing KIT V559D in culture (PMID: 21689725). 21689725
KIT V559D Advanced Solid Tumor sensitive Imatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT V559D were sensitive to Gleevec (imatinib), demonstrating decreased cell proliferation in culture and inhibition of Kit, Erk1/2, and Stat3 phosphorylation (PMID: 24205792). 24205792
KIT V559D Advanced Solid Tumor sensitive Imatinib Preclinical - Cell culture Actionable In a preclinical study, Gleevec (imatinib) decreased KIT signaling, and inhibited growth and induced apoptosis of transformed cells expressing KIT V559D in culture (PMID: 21689725). 21689725
KIT V559D KIT Y823D Advanced Solid Tumor sensitive Flumatinib Preclinical Actionable In a preclinical study, Flumatinib treatment in transformed cells co-expressing KIT N822K and KIT V559D demonstrated decreased cell proliferation and inhibition of Kit, Erk 1/2, and Stat3 phosphorylation in culture, and led to improved survival in mouse models (PMID: 24205792). 24205792
KIT V559D KIT Y823D Advanced Solid Tumor no benefit Imatinib Preclinical Actionable In a preclinical study, Gleevec (imatinib) treatment in a mouse model with cells expressing KIT V559D and KIT Y823D resulted in shortened survival (PMID: 24205792). 24205792
KIT V559D KIT Y823D Advanced Solid Tumor no benefit Sunitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing KIT Y823D and KIT V559D were insensitive to Sutent (sunitinib) in culture and in mouse models (PMID: 24205792). 24205792
KIT D820G KIT V559D Advanced Solid Tumor sensitive Flumatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing KIT D820G and KIT V559D were sensitive to Flumatinib in culture, demonstrating decreased cell proliferation (PMID: 24205792). 24205792
KIT P551_V555del gastrointestinal stromal tumor sensitive Sorafenib Preclinical - Pdx Actionable In a preclinical study, Nexavar (sorafenib) inhibited Erk signaling, induced apoptosis, resulted in tumor growth inhibition in patient derived xenograft models of gastrointestinal stromal tumor harboring KIT P551_V555del (PMID: 19139124). 19139124
KIT V555_L576del KIT D820G KIT D820Y gastrointestinal stromal tumor predicted - resistant Imatinib Case Reports/Case Series Actionable In a clinical study, KIT D820G and KIT D820Y were identified as secondary mutations in a patient with gastrointestinal stromal tumor harboring a primary KIT V555_L576del mutation, who developed resistance to Gleevec (imatinib) (PMID: 18488160). 18488160
KIT W557_K558del KIT D820G Advanced Solid Tumor sensitive Ponatinib Preclinical Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT D820G were sensitive to Iclusig (ponatinib) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT W557_K558del KIT D820G Advanced Solid Tumor resistant Imatinib Preclinical Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT D820G were resistant to Gleevec (imatinib) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT W557_K558del KIT D820G Advanced Solid Tumor resistant Sunitinib Preclinical Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT D820G were resistant to Sutent (sunitinib) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT W557_K558del KIT D820G Advanced Solid Tumor resistant Regorafenib Preclinical Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT D820G were resistant to Stivarga (regorafenib) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT P577del KIT W557Lfs*5 KIT D820G gastrointestinal stromal tumor sensitive Cabozantinib Preclinical - Pdx Actionable In a preclinical study, Cometriq (Cabometyx, cabozantinib) slowed tumor growth and decreased mitotic activity in a gastrointestinal stromal tumor patient derived xenograft (PDX) model harboring KIT mutations, P577del, W557Lfs*5, and D820G (PMID: 27777285). 27777285
KIT P577del KIT W557Lfs*5 KIT D820G gastrointestinal stromal tumor sensitive PLX9486 Preclinical - Pdx Actionable In a preclinical study, PLX9486 treatment decreased Mapk and Kit downstream signaling, resulted in tumor volume stabilization in patient-derived xenograft (PDX) models of gastrointestinal stromal tumor harboring KIT P577del, W557Lfs*5, and D820G (18th Annual BSMO Meeting, Feb 2016, abstract O5). detail...
KIT P577del KIT W557Lfs*5 KIT D820G gastrointestinal stromal tumor resistant Imatinib Preclinical - Pdx Actionable In a preclinical study, a gastrointestinal stromal tumor patient derived xenograft (PDX) model harboring KIT mutations, P577del, W557Lfs*5, and D820G, demonstrated resistance to treatment with Gleevec (imatinib) (PMID: 27777285). 27777285
KIT exon 13 gastrointestinal stromal tumor sensitive Imatinib + MK2206 Preclinical - Cell culture Actionable In a preclinical study, the combination of Gleevec (imatinib) and MK2206 demonstrated synergy in inhibiting growth of a gastrointestinal stromal tumor cell line harboring a KIT exon 13 mutation in culture (PMID: 27370604). 27370604
KIT exon 13 melanoma sensitive Nilotinib Phase II Actionable In a Phase II trial, Tasigna (nilotinib) treatment resulted in complete response in 5% (1/19) and partial response in 21% (4/19) of melanoma patients harboring KIT exon 11 or exon 13 mutations (PMID: 28843487; NCT01168050). 28843487
KIT exon 13 melanoma sensitive Nilotinib Phase II Actionable In a Phase II trial, Tasigna (nilotinib) resulted in an overall response rate of 26.2% (11/41), which included a partial response in 7.7% (1/13) of melanoma patients harboring KIT exon 13 mutations (PMID: 28327988). 28327988
KIT V559G Advanced Solid Tumor sensitive Axitinib Preclinical - Cell culture Actionable In a preclinical study, Inlyta (axitinib) inhibited KIT phosphorylation and proliferation of transformed cells expressing KIT V559G in culture (PMID: 31205508). 31205508
KIT exon 11 del gastrointestinal stromal tumor predicted - sensitive Imatinib Phase III Actionable In a Phase III trial, gastrointestinal stromal tumor patients harboring KIT exon 11 deletions or indels demonstrated improved improved recurrence-free survival (RFS) with 3-year adjuvant Gleevec (imatinib) treatment (5-year RFS, 70%), compared to patients receiving 1-year treatment (5-year RFS, 41.3%) (PMID: 28334365). 28334365
KIT exon 11 del gastrointestinal stromal tumor predicted - sensitive AZD3229 Preclinical - Cell line xenograft Actionable In a preclinical study, AZD3229 inhibited Kit signaling, resulted in tumor regression in cell line xenograft models of gastrointestinal stromal tumor harboring KIT exon 11 deletion mutation (Proceedings of the American Association for Cancer Research, Vol 60, Mar 2019, Abstract #1328). detail...
KIT H697Y Advanced Solid Tumor sensitive Sunitinib Preclinical Actionable In a preclinical study, Sutent (sunitinib) inhibited growth of transformed cell lines overexpressing KIT H697Y in culture (PMID: 19861435). 19861435
KIT H697Y Advanced Solid Tumor decreased response Imatinib Preclinical Actionable In a preclinical study, transformed cell lines overexpressing KIT H697Y demonstrated reduced sensitivity to Gleevec (imatinib mesylate)-induced growth inhibition in culture (PMID: 19861435). 19861435
KIT D820N gastrointestinal stromal tumor predicted - resistant Imatinib Case Reports/Case Series Actionable In a clinical study, KIT D820N was identified as a secondary mutation in the metastatic lesions from a gastrointestinal stromal tumor patient whose disease progressed on Gleevec (imatinib) (PMID: 18628470). 18628470
KIT D579del thymic carcinoma sensitive Imatinib Case Reports/Case Series Actionable In a clinical case study, a patient with thymic carcinoma harboring KIT D579del achieved disease stabilization following treatment with Gleevec (imatinib) (PMID: 24419427). 24419427
KIT S476I MET R988C gastrointestinal stromal tumor predicted - sensitive Bevacizumab + Sorafenib Case Reports/Case Series Actionable In a Phase I trial, a GIST patient harboring KIT S476I and MET R988C demonstrated sensitivity to the combination treatment, Nexavar (sorafenib) and Avastin (bevacizumab), resulting in stable disease for 6 months (PMID: 25363205). 25363205
KIT S476I mast-cell leukemia predicted - sensitive Nilotinib Preclinical - Patient cell culture Actionable In a preclinical study, treatment with Tasigna (nilotinib) decreased proliferation of patient-derived neoplastic mast cells harboring KIT S476I in culture (PMID: 25209843). 25209843
KIT S476I mast-cell leukemia predicted - sensitive Midostaurin Preclinical - Patient cell culture Actionable In a preclinical study, treatment with Rydapt (midostaurin) decreased proliferation of patient-derived neoplastic mast cells harboring KIT S476I in culture (PMID: 25209843). 25209843
KIT M552_V559del Advanced Solid Tumor sensitive Motesanib Preclinical - Cell culture Actionable In a preclinical study, Motesanib (AMG 706) inhibited KIT phosphorylation and growth of cells expressing KIT M552_V559del in culture (PMID: 20633291). 20633291
KIT N822K acute myeloid leukemia sensitive DCC-2618 Preclinical - Pdx Actionable In a preclinical study, DCC-2618 induced tumor regression in a patient-derived xenograft (PDX) model of acute myeloid leukemia harboring KIT N822K (Cancer Res 2015;75(15 Suppl):Abstract nr 2690). detail...
KIT N822K Advanced Solid Tumor resistant Imatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT N822K were resistant to treatment with Gleevec (imatinib) in culture (PMID: 24205792). 24205792
KIT N822K acute myeloid leukemia predicted - sensitive Sunitinib Preclinical - Cell culture Actionable In a preclinical study, an acute myeloid leukemia cell line harboring KIT N822K demonstrated increased sensitivity to Sutent (sunitinib) compared to cells with wild-type KIT, resulting in increased inhibition of colony formation, and induction of cell-cycle arrest, apoptosis, and autophagy in culture (PMID: 31217744). 31217744
KIT N822K acute myeloid leukemia sensitive Avapritinib Preclinical - Cell culture Actionable In a preclinical study, BLU-285 inhibited Kit phosphorylation and proliferation of acute myeloid leukemia cells harboring KIT N822K in culture (PMID: 29093181). 29093181
KIT N822K gastrointestinal stromal tumor predicted - resistant Imatinib Case Reports/Case Series Actionable In a clinical case study, KIT N822K was identified in the tumor of a gastrointestinal stromal tumor patient who was resistant to Gleevec (imatinib) treatment (PMID: 26316776). 26316776
KIT N822K Advanced Solid Tumor predicted - sensitive Sunitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT N822K were more sensitive to treatment with Sutent (sunitinib) in culture compared to Gleevec (imatinib), demonstrating decreased cell proliferation (PMID: 24205792). 24205792
KIT N822K Advanced Solid Tumor predicted - sensitive Flumatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT N822K were more sensitive to treatment with Flumatinib in culture compared to Gleevec (imatinib), demonstrating decreased cell proliferation (PMID: 24205792). 24205792
KIT N822K leukemia sensitive Ponatinib Preclinical - Cell culture Actionable In a preclinical study, Iclusig (ponatinib) inhibited Kit signaling and viability in leukemia cells harboring KIT N822K in culture (PMID: 21482694). 21482694
KIT N822K acute myeloid leukemia sensitive BPR1J373 Preclinical - Cell line xenograft Actionable In a preclinical study, an acute myeloid leukemia cell line harboring KIT N822K demonstrated sensitivity to treatment with BPR1J373, showing inhibition of Kit phosphorylation and apoptotic induction in culture, and tumor regression in xenograft models (PMID: 27512117). 27512117
KIT W557_K558del KIT N822K Advanced Solid Tumor resistant Imatinib Preclinical Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT N822K were resistant to Gleevec (imatinib) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT W557_K558del KIT N822K Advanced Solid Tumor resistant Sunitinib Preclinical Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT N822K were resistant to Sutent (sunitinb) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT W557_K558del KIT N822K Advanced Solid Tumor resistant Regorafenib Preclinical Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT N822K were resistant to Stivarga (regorafenib) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT W557_K558del KIT N822K Advanced Solid Tumor sensitive Ponatinib Preclinical Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT N822K were sensitive to Iclusig (ponatinib) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT W557_K558delinsCE KIT N822K gastrointestinal stromal tumor predicted - resistant Imatinib Case Reports/Case Series Actionable In a clinical study, KIT N822K was identified as a secondary mutation in a patient with gastrointestinal stromal tumor harboring a primary KIT W557_K558delinsCE mutation, who developed resistance to Gleevec (imatinib mesylate) (PMID: 18488160). 18488160
KIT A502_Y503dup KIT N822K gastrointestinal stromal tumor predicted - resistant Imatinib Case Reports/Case Series Actionable In a clinical study, KIT N822K was identified as a secondary mutation in a patient with gastrointestinal stromal tumor harboring a primary KIT A502_Y503dup mutation, who developed resistance to Gleevec (imatinib) (PMID: 18488160). 18488160
KIT amp PDGFRA amp glioblastoma multiforme sensitive DCC-2618 Phase I Actionable In a Phase I trial, DCC-2618 demonstrated preliminary safety and efficacy in patients with advanced solid tumors, including a partial response in a glioblastoma multiforme patient harboring KIT and PDGFRA amplification (EORTC-NCI-AACR 2016, Abs 7LBA). detail...
ROS1 fusion KDR amp KIT amp PDGFRA amp lung non-small cell carcinoma predicted - resistant Crizotinib Case Reports/Case Series Actionable In a clinical study, a non-small cell lung carcinoma patient harboring a ROS1 fusion treated with Xalkori (crizotinib) responded, but eventually progressed, and was subsequently found to harbor presumed resistance alterations, including amplification of KIT, KDR, and PDGFRA (PMID: 29636358). 29636358
ALK fusion ALK G1202R KIT amp lung non-small cell carcinoma predicted - resistant Crizotinib Case Reports/Case Series Actionable In a clinical study, an ALK G1202R secondary mutation as well as KIT amplification were identified in a patient with ALK fusion-positive non-small cell lung cancer with resistance to Xalkori (crizotinib) (PMID: 22277784). 22277784
KIT D816Y Advanced Solid Tumor resistant Flumatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT D816Y were resistant to treatment with Flumatinib in culture (PMID: 24205792). 24205792
KIT D816Y Advanced Solid Tumor resistant Sunitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT D816Y were resistant to treatment with Sutent (sunitinib) in culture (PMID: 24205792). 24205792
KIT D816Y Advanced Solid Tumor resistant Imatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT D816Y were resistant to treatment with Gleevec (imatinib) in culture (PMID: 24205792). 24205792
KIT D816Y Advanced Solid Tumor resistant Imatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT D816Y were resistant to Gleevec (imatinib mesylate) in culture (PMID: 16397263). 16397263
KIT D816Y mast cell neoplasm sensitive DCC-2618 Preclinical - Cell culture Actionable In a preclinical study, DCC-2618 inhibited proliferation of a mouse mastocytosis cell line expressing KIT K816Y in culture (Cancer Res 2015;75(15 Suppl):Abstract nr 2690). detail...
KIT D816Y mast cell neoplasm sensitive Avapritinib Preclinical Actionable In a preclinical study, BLU-285 inhibited Kit phosphorylation and proliferation of murine mastocytoma cells harboring KIT D814Y (corresponding to human D816Y) in culture, and resulted in tumor regression in allograft animal models (PMID: 29093181). 29093181
KIT exon 9 Advanced Solid Tumor sensitive Ponatinib Preclinical Actionable In a preclinical study, transformed cells expressing a KIT exon 9 mutation demonstrated sensitivity to treatment with Iclusig (ponatinib) in culture, resulting in reduced cell viability (PMID: 25239608). 25239608
KIT exon 9 Advanced Solid Tumor resistant Regorafenib Preclinical Actionable In a preclinical study, Stivarga (regorafineb) had no effect on transformed cells expressing a KIT exon 9 mutation in culture (PMID: 25239608). 25239608
KIT exon 9 Advanced Solid Tumor resistant Imatinib Preclinical Actionable In a preclinical study, Gleevec (imatinib) had no effect on transformed cells expressing a KIT exon 9 mutation in culture (PMID: 25239608). 25239608
KIT exon 9 gastrointestinal stromal tumor sensitive Imatinib Guideline Actionable Gleevec (imatinib) is included in the guidelines for patients with advanced/metastatic gastrointestinal stromal tumor (GIST) with KIT exon 9 mutations (PMID: 30188977; ESMO.org). 30188977 detail...
KIT exon 9 gastrointestinal stromal tumor sensitive Imatinib Guideline Actionable Gleevec (imatinib) is included in the guidelines as first-line therapy for patients with gastrointestinal stromal tumor (GIST) with KIT exon 9 mutations (NCCN.org). detail...
KIT exon 9 gastrointestinal stromal tumor predicted - sensitive Sunitinib Clinical Study - Cohort Actionable In a retrospective analysis, GIST patients with KIT exon 9 mutations showed improved progression-free survival (PFS), overall survival, and objective response rate (ORR) compared to patients with exon 11 mutations, with a median PFS of 12.3 months vs. 7.0 months, and an ORR of 19% (8/42) vs. 6% (9/143) following treatment with Sutent (sunitinib) (PMID: 26772734). 26772734
KIT exon 9 Advanced Solid Tumor sensitive Sunitinib Preclinical Actionable In a preclinical study, transformed cells expressing a KIT exon 9 mutation demonstrated sensitivity to treatment with Sutent (sunitinib) in culture, resulting in reduced cell viability (PMID: 25239608). 25239608
KIT V559del gastrointestinal stromal tumor sensitive G007-LK + Imatinib Preclinical Actionable In a preclinical study, the combination of G007-LK and Gleevec (imatinib) demonstrated increased anti-tumor activity compared to either agent alone in a mouse model of gastrointestinal stromal tumor expressing Kit V558del (corresponding to human V559del) (PMID: 28611108). 28611108
KIT D816G ROS1 fusion lung non-small cell carcinoma predicted - resistant Crizotinib Case Reports/Case Series Actionable In a clinical study, a non-small cell lung carcinoma patient harboring a ROS1 fusion developed resistance to treatment with Xalkori (crizotinib) and was subsequently found to have acquired KIT D816G (PMID: 29636358). 29636358
KIT W557_K558del KIT D816G Advanced Solid Tumor resistant Regorafenib Preclinical Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT D816G were resistant to Stivarga (regorafenib) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT W557_K558del KIT D816G Advanced Solid Tumor resistant Sunitinib Preclinical Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT D816G were resistant to Sutent (sunitinib) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT W557_K558del KIT D816G Advanced Solid Tumor resistant Imatinib Preclinical Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT D816G were resistant to Gleevec (imatinib) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT W557_K558del KIT D816G Advanced Solid Tumor resistant Ponatinib Preclinical Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT D816G were sensitive to Iclusig (ponatinib) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT T417_D419delinsI Advanced Solid Tumor sensitive Flumatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT T417_D419delinsI were sensitive to treatment with Flumatinib, demonstrating decreased cell proliferation (PMID: 24205792). 24205792
KIT T417_D419delinsI Advanced Solid Tumor conflicting Imatinib Preclinical - Cell culture Actionable In a preclinical study, Gleevec (imatinib mesylate) inhibited Kit phosphorylation in transformed cells over expressing KIT T417_D419delinsI in culture (PMID: 16015387). 16015387
KIT T417_D419delinsI Advanced Solid Tumor conflicting Imatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT T417_D419delinsI were resistant to treatment with Gleevec (imatinib) in culture (PMID: 24205792). 24205792
KIT T417_D419delinsI Advanced Solid Tumor sensitive Sunitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT T417_D419delinsI were sensitive to treatment with Sutent (sunitinib), demonstrating decreased cell proliferation (PMID: 24205792). 24205792
KIT K558delinsNP Advanced Solid Tumor sensitive Sunitinib Preclinical Actionable In a preclinical study, transformed cells expressing K558delinsNP demonstrated sensitivity to treatment with Sutent (sunitinib) in culture, resulting in reduced cell viability (PMID: 25239608). 25239608
KIT K558delinsNP Advanced Solid Tumor sensitive Regorafenib Preclinical Actionable In a preclinical study, transformed cells expressing K558delinsNP demonstrated sensitivity to treatment with Stivarga (regorafenib) in culture, resulting in reduced cell viability (PMID: 25239608). 25239608
KIT K558delinsNP Advanced Solid Tumor sensitive Ponatinib Preclinical Actionable In a preclinical study, transformed cells expressing KIT K558delinsNP demonstrated sensitivity to treatment with Iclusig (ponatinib) in culture, resulting in reduced cell viability (PMID: 25239608). 25239608
KIT K558delinsNP Advanced Solid Tumor sensitive Imatinib Preclinical Actionable In a preclinical study, transformed cells expressing KIT K558delinsNP demonstrated sensitivity to treatment with Gleevec (imatinib) in culture, resulting in reduced cell viability (PMID: 25239608). 25239608
KIT Y578C Advanced Solid Tumor sensitive Imatinib Preclinical Actionable In a preclinical study, Gleevec (imatinib mesylate) inhibited Kit phosphorylation efficiently in transformed human cells over expressing KIT Y578C in culture (PMID: 23567324). 23567324
KIT W557C KIT Y578C Advanced Solid Tumor sensitive Imatinib Preclinical Actionable In a preclinical study, Gleevec (imatinib mesylate) inhibited Kit phosphorylation efficiently in transformed human cells over expressing both KIT W557C and KIT Y578C in culture (PMID: 23567324). 23567324
KIT V559_V560del Advanced Solid Tumor sensitive Imatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT V559_V560del were sensitive to Gleevec (imatinib), demonstrating decreased cell proliferation in culture (PMID: 24205792). 24205792
KIT V559_V560del Advanced Solid Tumor sensitive Flumatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT V559_V560del were sensitive to Flumatinib, demonstrating decreased cell proliferation in culture (PMID: 24205792). 24205792
KIT V559_V560del Advanced Solid Tumor sensitive Sunitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT V559_V560del were sensitive to Sutent (sunitinib), demonstrating decreased cell proliferation in culture (PMID: 24205792). 24205792
KIT K558_G565delinsR gastrointestinal stromal tumor sensitive Imatinib Preclinical - Pdx Actionable In a preclinical study, Gleevec (imatinib) treatment resulted in tumor regression and decreased mitotic activity in gastrointestinal stromal tumor patient derived xenograft (PDX) models harboring KIT K558_G565delinsR (PMID: 27777285). 27777285
KIT K558_G565delinsR gastrointestinal stromal tumor sensitive Cabozantinib Preclinical - Pdx Actionable In a preclinical study, Cometriq (Cabometyx, cabozantinib) resulted in tumor regression, decreased mitotic activity, and increased apoptotic activity in a gastrointestinal stromal tumor patient derived xenograft (PDX) model harboring KIT K558_G565delins (PMID: 27777285). 27777285
KIT A502_Y503dup KIT D820E gastrointestinal stromal tumor predicted - resistant Sunitinib Preclinical - Pdx Actionable In a preclinical study, Sutent (sunitinib) did not inhibit Kit, Erk, or Mtor signaling and resulted in minimal (26.2%) tumor inhibition in patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT A502_Y503dup and KIT D820E, which was established from a patient who did not respond to Gleevec (imatinib mesylate) and Sutent (sunitinib) (PMID: 29100343). 29100343
KIT A502_Y503dup KIT D820E gastrointestinal stromal tumor resistant Imatinib Preclinical - Pdx Actionable In a preclinical study, Gleevec (imatinib mesylate) did not inhibit Kit, Erk, or Mtor signaling and resulted in minimal (7.4%) tumor inhibition in patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT A502_Y503dup and KIT D820E, which was established from a patient who did not respond to Gleevec (imatinib mesylate) and Sutent (sunitinib) (PMID: 29100343). 29100343
KIT D820E thymic carcinoma predicted - sensitive Sorafenib Case Reports/Case Series Actionable In a clinical case study, a patient with metastatic thymic carcinoma harboring KIT D820E demonstrated a partial response to treatment with Nexavar (sorafenib) (PMID: 19461405). 19461405
KIT D820E Advanced Solid Tumor sensitive Ponatinib Preclinical Actionable In a preclinical study, cells expressing KIT D820E demonstrated sensitivity to Iclusig (ponatinib) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT K550_W557del Advanced Solid Tumor sensitive Imatinib Preclinical Actionable In a preclinical study, transformed cells expressing KIT K550_W557del demonstrated sensitivity to treatment with Gleevec (imatinib) in culture, resulting in reduced cell viability (PMID: 25239608). 25239608
KIT K550_W557del Advanced Solid Tumor sensitive Regorafenib Preclinical Actionable In a preclinical study, transformed cells expressing KIT K550_W557del demonstrated sensitivity to treatment with Stivarga (regorafenib) in culture, resulting in reduced cell viability (PMID: 25239608). 25239608
KIT K550_W557del Advanced Solid Tumor sensitive Ponatinib Preclinical Actionable In a preclinical study, transformed cells expressing KIT K550_W557del demonstrated sensitivity to treatment with Iclusig (ponatinib) in culture, resulting in reduced cell viability (PMID: 25239608). 25239608
KIT K550_W557del Advanced Solid Tumor sensitive Sunitinib Preclinical Actionable In a preclinical study, transformed cells expressing KIT K550_W557del demonstrated sensitivity to treatment with Sutent (sunitinib) in culture, resulting in reduced cell viability (PMID: 25239608). 25239608
KIT M552_K558del gastrointestinal stromal tumor predicted - resistant Ponatinib Case Reports/Case Series Actionable In a clinical study, a GIST patient harboring KIT M552_K558del, resistant to multiple tyrosine kinase inhibitors, demonstrated resistance to Iclusig (ponatinib) treatment as indicated by disease progression after 4 weeks of treatment (PMID: 25239608). 25239608
KIT Y553S KIT V556_T574del KIT D820Y gastrointestinal stromal tumor predicted - resistant Imatinib Case Reports/Case Series Actionable In a clinical study, KIT D820Y was identified as a secondary mutation in a patient with gastrointestinal stromal tumor harboring primary KIT V569_L576del and KIT Y553S mutations, who developed resistance to Gleevec (imatinib) (PMID: 18488160). 18488160
KIT N822I Advanced Solid Tumor resistant Imatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT N822I demonstrated resistance to Gleevec (imatinib) in culture (PMID: 21689725). 21689725
KIT N822I Advanced Solid Tumor sensitive Dasatinib Preclinical - Cell culture Actionable In a preclinical study, Sprycel (dasatinib) inhibited growth and induced apoptosis of transformed cells expressing KIT N822I in culture (PMID: 21689725). 21689725
KIT K558_V560del KIT W557C gastrointestinal stromal tumor predicted - sensitive Ponatinib Case Reports/Case Series Actionable In a clinical study, a GIST patient harboring KIT K558_V560del and KIT W557C, resistant to Gleevec (imatinib), Sutent (sunitinib), and Stivarga (regorafenib), demonstrated sensitivity when treated with Iclusig (ponatinib), which resulted in a radiologic response and stabilization for six months (PMID: 25239608). 25239608
KIT T632I melanoma predicted - resistant Imatinib Case Reports/Case Series Actionable In a clinical case study, Gleevec (imatinib) treatment resulted in worsened condition and continued disease progression and metastasis in a patient with metastatic melanoma harboring KIT T632I (PMID: 31043947). 31043947
KIT exon 11 gastrointestinal stromal tumor predicted - sensitive Pexidartinib + PLX9486 Phase I Actionable In a Phase I trial, PLX9486 and Pexidartinib (PLX3397) combination therapy demonstrated safety and preliminary efficacy, resulted in a partial response rate of 8.3% (1/12) and progression-free survival not yet reached in patients with advanced solid tumors, 11 of these patients had gastrointestinal stromal tumor that progressed on Gleevec (imatinib mesylate), and most harbored KIT exon 11 and exon 17 mutations (Journal of Clinical Oncology 36, no. 15_suppl (May 20 2018) 11509-11509; NCT02401815). detail...
KIT exon 11 gastrointestinal stromal tumor sensitive Imatinib + XAV939 Preclinical - Cell culture Actionable In a preclinical study, treatment with the combination of XAV939 and Gleevec (imatinib) resulted in decreased viability of gastrointestinal stromal tumor (GIST) cell lines harboring KIT exon 11 mutations compared to Gleevec (imatinib) alone, in culture (PMID: 28611108). 28611108
KIT exon 11 melanoma predicted - sensitive Imatinib Case Reports/Case Series Actionable In a clinical case study, Gleevec (imatinib) treatment resulted in a partial response in a patient with metastastic anal melanoma harboring a 21 base-pair duplication in KIT exon 11, and reduced pulmonary metastasis by 60% (PMID: 20372153). 20372153
KIT exon 11 gastrointestinal stromal tumor sensitive Imatinib + PKF118-310 Preclinical - Cell culture Actionable In a preclinical study, treatment with the combination of PKF118-310 and Gleevec (imatinib) resulted in decreased viability of gastrointestinal stromal tumor (GIST) cell lines harboring KIT exon 11 mutations compared to Gleevec (imatinib) alone, in culture (PMID: 28611108). 28611108
KIT exon 11 gastrointestinal stromal tumor predicted - sensitive Ponatinib Phase II Actionable In a Phase II trial, Iclusig (ponatinib) treatment resulted in partial response in 7% (2/27), stable disease in 59% (16/27), a median progression free survival of 4.3 months and a median overall survival of 15.0 months in gastrointestinal stromal tumor patients harboring KIT exon 11 mutations after prior tyrosine kinase inhibitor treatment failure (J Clin Oncol 33, 2015 (suppl; abstr 10535)). detail...
KIT exon 11 gastrointestinal stromal tumor decreased response Sunitinib Clinical Study - Cohort Actionable In a retrospective analysis, GIST patients with KIT exon 11 mutations showed decreased benefit compared to patients with exon 9 mutations, with median PFS of 7.0 months with exon 11 mutations vs. 12.3 months with exon 9 mutations, and an ORR of 6% (9/143) vs. 19% (8/42) following treatment with Sutent (sunitinib) (PMID: 26772734). 26772734
KIT exon 11 gastrointestinal stromal tumor sensitive Nilotinib Phase III Actionable In a Phase III trial, a 24 month progression free survival was observed in 69.6% of advanced GIST patients harboring KIT exon 11 mutations when treated with Tasigna (nilotinib) (J Clin Oncol May 2013 vol. 31 no. 15_suppl 10501). detail...
KIT exon 11 gastrointestinal stromal tumor sensitive Regorafenib Phase II Actionable In a Phase II clinical trial, treatment with Stivarga (regorafenib) resulted in a clinical benefit rate of 76% (25/33), a median progression-free survival (PFS) of 13.2 months, and a median overall survival of 25 months in patients with gastrointestinal stromal tumors, with patients with KIT exon 11 mutations demonstrating the longest PFS of 13.4 months (PMID: 27371698). 27371698
KIT exon 11 gastrointestinal stromal tumor sensitive Imatinib + MK2206 Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Gleevec (imatinib) and MK2206 increased growth inhibition and decreased viability of gastrointestinal stromal tumor (GIST) cell lines harboring KIT exon 11 mutations in culture, and improved survival and inhibited tumor growth in a KIT exon 11-mutant GIST cell line xenograft model, with increased efficacy compared to either agent alone (PMID: 27370604). 27370604
KIT exon 11 gastrointestinal stromal tumor sensitive Imatinib Phase III Actionable In a Phase III trial, a long-term analysis of gastrointestinal stromal tumor (GIST) patients treated with Gleevec (imatinib) demonstrated patients harboring KIT exon 11 mutations had a median progression-free survival of 39.4 months, and median overall survival was not reached, with 69.1% of patients with KIT exon 11 mutations alive at 5 years (PMID: 26687836; NCT00367861). 26687836
KIT exon 11 gastrointestinal stromal tumor sensitive Imatinib Guideline Actionable Gleevec (imatinib) is included in the guidelines as first-line therapy for patients with gastrointestinal stromal tumor (GIST) with KIT exon 11 mutations (NCCN.org). detail...
KIT exon 11 gastrointestinal stromal tumor sensitive Imatinib Phase III Actionable In a Phase III trial, Gleevec (imatinib) treatment resulted in longer overall survival (OS) (66 vs 40 months) in gastrointestinal stromal tumor (GIST) patients harboring KIT exon 11 mutations compared to KIT and PDGFRA wild-type patients, while subtypes of KIT exon 11 mutations (deletion, insertation/duplication, point mutation) did not affect OS outcome (PMID: 28196207; NCT00009906). 28196207
KIT exon 11 gastrointestinal stromal tumor sensitive Imatinib Guideline Actionable Gleevec (imatinib) is included in the guidelines for patients with advanced/metastatic gastrointestinal stromal tumor (GIST) with KIT exon 11 mutations (PMID: 30188977; ESMO.org). 30188977 detail...
KIT exon 11 melanoma sensitive Nilotinib Phase II Actionable In a Phase II trial, Tasigna (nilotinib) resulted in an overall response rate of 26.2% (11/41), which included a partial response of 38.5% (10/26) and a progression free survival of 5.4 months in melanoma patients harboring KIT exon 11 mutations (PMID: 28327988). 28327988
KIT exon 11 melanoma sensitive Nilotinib Phase II Actionable In a Phase II trial, Tasigna (nilotinib) treatment resulted in complete response in 5% (1/19) and partial response in 21% (4/19) of melanoma patients harboring KIT exon 11 or exon 13 mutations (PMID: 28843487; NCT01168050). 28843487
KIT exon 11 gastrointestinal stromal tumor predicted - sensitive DCC-2618 Preclinical - Cell line xenograft Actionable In a preclinical study, DCC-2618 inhibited Kit phosphorylation and tumor growth in a gastrointestinal stromal tumor cell line xenograft model harboring a KIT exon 11 deletion mutation (Cancer Res 2015;75(15 Suppl):Abstract nr 2690). detail...
KIT exon 11 gastrointestinal stromal tumor predicted - sensitive Dasatinib Phase II Actionable In a Phase II clinical trial, Sprycel (dasatinib) demonstrated preliminary activity in patients with Gleevec (imatinib)-resistant gastrointestinal stromal tumor (GIST), including patients harboring KIT exon 11 mutations, with a partial response rate of 32% (15/47), median progression-free survival of 2.0 months, and overall survival of 19 months (J Clin Oncol 29: 2011 (suppl; abstr 10006)). detail...
KIT exon 11 gastrointestinal stromal tumor predicted - sensitive PLX9486 Phase I Actionable In a Phase I trial, PLX9486 demonstrated safety and preliminary efficacy, resulted in a progression-free survival of more than 24 weeks and partial response in 8.3% (2/24) of patients with advanced solid tumors, 20 of these patients had gastrointestinal stromal tumor that progressed on Gleevec (imatinib mesylate), and most harbored KIT exon 11 and exon 17 mutations (Journal of Clinical Oncology 36, no. 15_suppl (May 20 2018) 11509-11509; NCT02401815). detail...
KIT exon 11 KIT exon 17 gastrointestinal stromal tumor predicted - sensitive PLX9486 Phase I Actionable In a Phase I trial, PLX9486 treatment resulted in partial response with 33% decrease of tumor size after 4 cycles of therapy in a patient with gastrointestinal stromal tumor harboring a primary KIT exon 11 mutation and a secondary KIT exon 17 mutation, who progressed on prior Gleevec (imatinib mesylate) and Sutent (sunitinib) therapies (CTOS Annual Meeting, Nov 2017, abstract # 2771952). detail...
KIT exon 11 KIT A829P gastrointestinal stromal tumor sensitive Imatinib + MK2206 Preclinical - Cell culture Actionable In a preclinical study, the combination of Gleevec (imatinib) and MK2206 demonstrated synergy in inhibiting growth of a Gleevec (imatinib)-resistant gastrointestinal stromal tumor cell line harboring a KIT exon 11 mutation and KIT A829P in culture (PMID: 27370604). 27370604
KIT exon 11 KIT T670I gastrointestinal stromal tumor predicted - sensitive Sunitinib Preclinical - Pdx Actionable In a preclinical study, Sutent (sunitinib) inhibited Kit signaling, resulted in 86.7% tumor growth inhibition in patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT exon 11 mutation (K550_splice) and KIT T670I, which was established from a patient who did not respond to Gleevec (imatinib mesylate) (PMID: 29100343). 29100343
KIT exon 11 KIT T670I gastrointestinal stromal tumor resistant Imatinib Preclinical - Pdx Actionable In a preclinical study, Gleevec (imatinib mesylate) did not inhibit Kit, Erk signaling and resulted in limited (53.9%) tumor inhibition in patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT exon 11 mutation (K550_splice) and KIT T670I, which was established from a patient who did not respond to Gleevec (imatinib mesylate) (PMID: 29100343). 29100343
KIT exon 11 KIT T670I gastrointestinal stromal tumor predicted - sensitive Regorafenib Preclinical - Pdx Actionable In a preclinical study, Stivarga (regorafenib) inhibited Kit signaling, resulted in tumor growth inhibition in patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT exon 11 mutation (K550_splice) and KIT T670I, which was established from a patient who did not respond to Gleevec (imatinib mesylate) (PMID: 29100343). 29100343
KIT positive prostate neuroendocrine neoplasm no benefit Imatinib Preclinical Actionable In a preclinical study, a prostate neuroendocrine tumor mouse model expressing Kit did not respond to Gleevec (imatinib), a result of impaired signaling of the Kit pathway (PMID: 27980106). 27980106
KIT positive germ cell cancer resistant Imatinib Phase II Actionable In a small Phase II study, 18 patients with KIT-positive refractory germ cell tumors treated with Gleevec (imatinib) experienced no significant antitumor activity (PMID: 16462496). 16462496
KIT positive breast cancer predicted - sensitive Imatinib + Letrozole Phase 0 Actionable In a pilot trial, Gleevec (imatinib mesylate) and Femara (letrozole) combination treatment resulted in clinical partial response in 90% (9/10) and stable disease in 10% (1/10) of the evaluable patients with invasive hormone-sensitive breast cancer, 8 of the 13 enrolled patients had KIT-positive tumors (PMID: 18248884). 18248884
KIT positive gastrointestinal stromal tumor sensitive Imatinib FDA approved Actionable In a Phase II trial that supported FDA approval, treatment with Gleevec (imatinib) resulted in an overall response rate of 38% (56/147) and a median duration of response of 13 weeks in patients with metastatic or unresectable KIT-positive GIST (PMID: 12374669). 12374669 detail...
KIT A502_Y503dup PDGFRA H687Y gastrointestinal stromal tumor predicted - resistant Imatinib Case Reports/Case Series Actionable In a clinical study, PDGFRA H687Y was identified as a secondary mutation in a patient with gastrointestinal stromal tumor harboring primary KIT A502_Y503dup mutation, who developed resistance to Gleevec (imatinib mesylate) (PMID: 18488160). 18488160
KIT A502_Y503dup gastrointestinal stromal tumor resistant Imatinib Preclinical - Pdx Actionable In a preclinical study, a gastrointestinal stromal tumor patient derived xenograft (PDX) model harboring KIT A502_Y503dup demonstrated resistance to treatment with Gleevec (imatinib), resulting in increased tumor volume (PMID: 27777285). 27777285
KIT A502_Y503dup gastrointestinal stromal tumor predicted - sensitive Regorafenib Preclinical - Pdx Actionable In a preclinical study, Stivarga (regorafenib) did not significantly inhibit Kit, Erk, or Mtor signaling, but resulted in tumor growth inhibition in patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT A502_Y503dup and KIT D820E, which was established from a patient who did not respond to Gleevec (imatinib mesylate) and Sutent (sunitinib) (PMID: 29100343). 29100343
KIT A502_Y503dup Advanced Solid Tumor sensitive Flumatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT A502_Y503dup (Y503_F504insAY) were sensitive to Flumatinib in culture, demonstrating decreased cell proliferation (PMID: 24205792). 24205792
KIT A502_Y503dup gastrointestinal stromal tumor sensitive Cabozantinib Preclinical - Pdx Actionable In a preclinical study, Cometriq (Cabometyx, cabozantinib) resulted in decreased tumor volume and reduced mitotic activity in a gastrointestinal stromal tumor patient derived xenograft (PDX) model harboring KIT A502_Y503dup (PMID: 27777285). 27777285
KIT A502_Y503dup Advanced Solid Tumor sensitive Sunitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT A502_Y503dup (Y503_F504insAY) were sensitive to Sutent (sunitinib) in culture, demonstrating decreased cell proliferation (PMID: 24205792). 24205792
KIT A502_Y503dup Advanced Solid Tumor sensitive Imatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT A502_Y503dup (Y503_F504insAY) were sensitive to Gleevec (imatinib) in culture, demonstrating decreased cell proliferation (PMID: 24205792). 24205792
KIT W557G Advanced Solid Tumor sensitive Imatinib Preclinical Actionable In a preclinical study, Gleevec (imatinib mesylate) inhibited Kit phosphorylation efficiently in transformed human cells over expressing KIT W557G in culture (PMID: 23567324). 23567324
KIT P551_W557delinsL gastrointestinal stromal tumor predicted - sensitive Ponatinib Case Reports/Case Series Actionable In a clinical study, a GIST patient harboring KIT P551_W557delinsL, resistant to Gleevec (imatinib), Sutent (sunitinib), and Stivarga (regorafenib), demonstrated sensitivity to Iclusig (ponatinib) treatment, which resulted in tumor regression and stable disease (PMID: 25239608). 25239608
KIT V560_Y578del KIT D816E gastrointestinal stromal tumor decreased response Sunitinib Preclinical Actionable In a preclinical study, a patient derived GIST cell line co-harboring KIT V560_Y578del and KIT D816E demonstrated a decreased response to treatment with Sutent (sunitinib) (PMID: 25239608). 25239608
KIT D816E KIT Y570_L576del PTEN T321fs gastrointestinal stromal tumor sensitive Regorafenib Preclinical - Pdx Actionable In a preclinical study, Stivarga (regorafenib) inhibited Kit, Erk, and Mtor signaling, resulted in tumor growth inhibition in patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT D816E, KIT Y570_L576del, and PTEN T321fs, which was established from a patient who did not respond to Gleevec (imatinib mesylate), Sutent (sunitinib), and Nexavar (sorafenib) (PMID: 29100343). 29100343
KIT D816E KIT Y570_L576del PTEN T321fs gastrointestinal stromal tumor sensitive Imatinib + LY294002 Preclinical - Pdx Actionable In a preclinical study, Gleevec (imatinib mesylate) in combination with LY394002 resulted in enhanced tumor growth inhibition compared to monotherapy in patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT D816E, KIT Y570_L576del, and PTEN T321fs, which was established from a patient who did not respond to Gleevec (imatinib mesylate), Sutent (sunitinib), and Nexavar (sorafenib) (PMID: 29100343). 29100343
KIT D816E KIT Y570_L576del PTEN T321fs gastrointestinal stromal tumor resistant Imatinib Preclinical - Pdx Actionable In a preclinical study, Gleevec (imatinib mesylate) did not inhibit Kit, Erk, or Mtor signaling and resulted in minimal tumor inhibition in patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT D816E, KIT Y570_L576del, and PTEN T321fs, which was established from a patient who did not respond to Gleevec (imatinib mesylate), Sutent (sunitinib), and Nexavar (sorafenib) (PMID: 29100343). 29100343
KIT D816E KIT Y570_L576del PTEN T321fs gastrointestinal stromal tumor resistant Sunitinib Preclinical - Pdx Actionable In a preclinical study, Sutent (sunitinib) demonstrated limited inhibition of Kit, Erk, and Mtor signaling and resulted in minimal (22.9%) tumor inhibition in patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT D816E, KIT Y570_L576del, and PTEN T321fs, which was established from a patient who did not respond to Gleevec (imatinib mesylate), Sutent (sunitinib), and Nexavar (sorafenib) (PMID: 29100343). 29100343
KIT exon 17 gastrointestinal stromal tumor sensitive Avapritinib Phase I Actionable In a Phase I trial, BLU-285 demonstrated preliminary antitumor activity in gastrointestinal stromal tumor patients harboring KIT mutations, with reduced tumor burden in 38% (5/13) of patients, including 1 partial response and 4 stable diseases, and 3 of the 5 responding patients harbored KIT exon 17 mutations (EORTC-NCI-AACR 2016, Abs 6LBA). detail...
KIT exon 17 Advanced Solid Tumor sensitive Avapritinib Preclinical Actionable In a preclinical study, BLU-285 inhibited Kit phosphorylation and proliferation of various tumor cell lines harboring KIT exon 17 mutations in culture, and induced tumor regression in an allograft animal model (PMID: 29093181). 29093181
KIT exon 17 gastrointestinal stromal tumor predicted - sensitive Pexidartinib + PLX9486 Phase I Actionable In a Phase I trial, PLX9486 and Pexidartinib (PLX3397) combination therapy demonstrated safety and preliminary efficacy, resulted in a partial response rate of 8.3% (1/12) and progression-free survival not yet reached in patients with advanced solid tumors, 11 of these patients had gastrointestinal stromal tumor that progressed on Gleevec (imatinib mesylate), and most harbored KIT exon 11 and exon 17 mutations (Journal of Clinical Oncology 36, no. 15_suppl (May 20 2018) 11509-11509; NCT02401815). detail...
KIT exon 17 gastrointestinal stromal tumor predicted - sensitive PLX9486 Phase I Actionable In a Phase I trial, PLX9486 demonstrated safety and preliminary efficacy, resulted in a progression-free survival of more than 24 weeks and partial response in 8.3% (2/24) of patients with advanced solid tumors, 20 of these patients had gastrointestinal stromal tumor that progressed on Gleevec (imatinib mesylate), and most harbored KIT exon 11 and exon 17 mutations (Journal of Clinical Oncology 36, no. 15_suppl (May 20 2018) 11509-11509; NCT02401815). detail...
KIT D820Y melanoma predicted - sensitive Sorafenib Case Reports/Case Series Actionable In a clinical case study, Nexavar (sorafenib) treatment resulted in stable disease with 27% reduction in target lesions at 4 weeks in a patient with anal melanoma and pulmonary metastases harboring KIT D820Y (PMID: 20372153). 20372153
KIT D820Y melanoma sensitive Dasatinib Preclinical - Cell culture Actionable In a preclinical study, Sprycel (dasatinib) inhibited MNK pathway activation and proliferation of melanoma cell lines harboring KIT D820Y in culture (PMID: 29035277). 29035277
KIT D820Y melanoma resistant Imatinib Preclinical - Cell culture Actionable In a preclinical study, Gleevec (imatinib mesylate) failed to inhibit MNK pathway activation and proliferation of melanoma cell lines harboring KIT D820Y in culture (PMID: 29035277). 29035277
KIT D820Y melanoma sensitive SEL201 Preclinical - Cell line xenograft Actionable In a preclinical study, SEL201 inhibited MNK pathway signaling and growth of melanoma cell lines harboring KIT D820Y in culture, and suppressed tumor metastasis in xenograft models (PMID: 29035277). 29035277
KIT W557_K558del KIT Y823D gastrointestinal stromal tumor sensitive Ponatinib Preclinical - Pdx & cell culture Actionable In a preclinical study, a patient derived GIST cell line co-harboring KIT W557_K558del and KIT Y823D demonstrated sensitivity to Iclusig (ponatinib) in a PDX model, resulting in complete tumor regression (PMID: 25239608). 25239608
KIT W557_K558del KIT Y823D gastrointestinal stromal tumor sensitive Avapritinib Preclinical - Pdx Actionable In a preclinical study, BLU-285 inhibited Kit phosphorylation and resulted in tumor regression in patient-derived xenograft models of Gleevec (imatinib mesylate)-resistant gastrointestinal stromal tumor harboring KIT W557_K558del and Y823D (PMID: 29093181). 29093181
KIT W557_K558del KIT Y823D gastrointestinal stromal tumor sensitive DCC-2618 Preclinical - Pdx Actionable In a preclinical study, DCC-2618 induced tumor regression in a patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT W557_K558del and KIT Y823D (Cancer Res 2015;75(15 Suppl):Abstract nr 2690). detail...
KIT Y823D Advanced Solid Tumor sensitive Motesanib Preclinical - Cell culture Actionable In a preclinical study, Motesanib (AMG 706) inhibited KIT phosphorylation and growth of cells expressing KIT Y823D in culture (PMID: 20633291). 20633291
KIT Y823D gastrointestinal stromal tumor predicted - sensitive AZD3229 Preclinical - Pdx Actionable In a preclinical study, AZD3229 inhibited Kit signaling, resulted in tumor regression in patient-derived xenograft (PDX) models of gastrointestinal stromal tumor harboring KIT Y823D (Proceedings of the American Association for Cancer Research, Vol 60, Mar 2019, Abstract #1328). detail...
KIT W557_K558del Advanced Solid Tumor sensitive Imatinib Preclinical Actionable In a preclinical study, transformed cells expressing KIT W557_K558del demonstrated sensitivity to treatment with Gleevec (imatinib) in culture, resulting in reduced cell viability (PMID: 25239608). 25239608
KIT W557_K558del Advanced Solid Tumor sensitive Dasatinib Preclinical - Cell culture Actionable In a preclinical study, Sprycel (dasatinib) inhibited growth and induced apoptosis of transformed cells expressing KIT W557_K558del in culture (PMID: 17699867). 17699867
KIT W557_K558del Advanced Solid Tumor sensitive Nilotinib Preclinical - Cell culture Actionable In a preclinical study, Tasigna (nilotinib) inhibited growth of transformed cells expressing KIT W557_K558del in culture (PMID: 17699867). 17699867
KIT W557_K558del gastrointestinal stromal tumor sensitive PD-0325901 Preclinical - Cell culture Actionable In a preclinical study, PD-0325901 treatment inhibited Erk phosphorylation and decreased expression of ETV1 and CXCR4 in gastrointestinal stromal tumor cells harboring KIT W557_K558del (PMID: 26936919). 26936919
KIT W557_K558del Advanced Solid Tumor sensitive Regorafenib Preclinical Actionable In a preclinical study, transformed cells expressing KIT W557_K558del demonstrated sensitivity to treatment with Stivarga (regorafineb) in culture, resulting in reduced cell viability (PMID: 25239608). 25239608
KIT W557_K558del Advanced Solid Tumor sensitive Ponatinib Preclinical - Cell line xenograft Actionable In a preclinical study, transformed cells expressing KIT W557_K558del demonstrated sensitivity to treatment with Iclusig (ponatinib) in both culture and cell line xenograft models, resulting in reduced cell viability and near complete tumor regression (PMID: 25239608). 25239608
KIT W557_K558del Advanced Solid Tumor sensitive Sunitinib Preclinical Actionable In a preclinical study, transformed cells expressing W557_K558del demonstrated sensitivity to treatment with Sutent (sunitinib) in culture, resulting in reduced cell viability (PMID: 25239608). 25239608
KIT W557_K558del KIT A829P Advanced Solid Tumor resistant Imatinib Preclinical Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT A829P were resistant to Gleevec (imatinib) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT W557_K558del KIT A829P Advanced Solid Tumor resistant Regorafenib Preclinical Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT A829P were resistant to Stivarga (regorafenib) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT W557_K558del KIT A829P Advanced Solid Tumor sensitive Ponatinib Preclinical Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT A829P were sensitive to Iclusig (ponatinib) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT W557_K558del KIT A829P Advanced Solid Tumor resistant Sunitinib Preclinical Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT A829P were resistant to Sutent (sunitinb) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT W557_K558del KIT D816H Advanced Solid Tumor decreased response Imatinib Preclinical - Cell line xenograft Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT D816H demonstrated a decreased response to treatment with Gleevec (imatinib) in both culture and xenograft models, resulting in only a slight decrease in tumor volume (PMID: 25239608). 25239608
KIT W557_K558del KIT D816H Advanced Solid Tumor decreased response Sunitinib Preclinical - Cell line xenograft Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT D816H demonstrated a decreased response to treatment with Sutent (sunitinib) in both culture and cell line xenograft models, resulting in only a slight decrease in tumor volume (PMID: 25239608). 25239608
KIT W557_K558del KIT D816H Advanced Solid Tumor sensitive Ponatinib Preclinical - Cell line xenograft Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT D816H demonstrated sensitivity to treatment with Iclusig (ponatinib) in both culture and cell line xenograft models, resulting in reduced cell viability and tumor regression (PMID: 25239608). 25239608
KIT W557_K558del KIT D816H Advanced Solid Tumor decreased response Regorafenib Preclinical Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT D816H demonstrated a decreased response to treatment with Stivarga (regorafenib) in culture (PMID: 25239608). 25239608
KIT W557_K558del KIT D820A Advanced Solid Tumor resistant Regorafenib Preclinical Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT D820A were resistant to Stivarga (regorafenib) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT W557_K558del KIT D820A Advanced Solid Tumor resistant Imatinib Preclinical Actionable In a preclinical study, transformed cells co-expressing W557_K558del and KIT D820A were resistant to Gleevec (imatinib) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT W557_K558del KIT D820A Advanced Solid Tumor resistant Sunitinib Preclinical Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT D820A were resistant to Sutent (sunitinib) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT W557_K558del KIT D820A Advanced Solid Tumor sensitive Ponatinib Preclinical Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT D820A were sensitive to Iclusig (ponatinib) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT W557_K558del KIT T670I Advanced Solid Tumor resistant Dasatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing a KIT W557_K558del/T670I double mutation demonstrated resistance to Sprycel (dasatinib) in culture (PMID: 17699867). 17699867
KIT W557_K558del KIT T670I Advanced Solid Tumor resistant Nilotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing a KIT W557_K558del/T670I double mutation demonstrated resistance to Tasigna (nilotinib) in culture (PMID: 17699867). 17699867
KIT W557_K558del KIT T670I Advanced Solid Tumor no benefit Imatinib Preclinical - Cell line xenograft Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT T670I demonstrated no response to treatment with Gleevec (imatinib) in both culture and xenograft models (PMID: 25239608). 25239608
KIT W557_K558del KIT T670I Advanced Solid Tumor sensitive Ponatinib Preclinical Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT T670I demonstrated sensitivity to treatment with Iclusig (ponatinib) in both culture and cell line xenograft models, resulting in reduced cell viability and decreased tumor volume (PMID: 25239608). 25239608
KIT W557_K558del KIT T670I Advanced Solid Tumor sensitive Sunitinib Preclinical - Cell line xenograft Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT T670I demonstrated sensitivity to treatment with Sutent (sunitinib) in both culture and cell line xenograft models, resulting in reduced cell viability, decreased tumor volume, and tumor regression (PMID: 25239608). 25239608
KIT W557_K558del KIT T670I Advanced Solid Tumor sensitive Sorafenib Preclinical - Cell culture Actionable In a preclinical study, Nexavar (sorafenib) inhibited proliferation and induced apoptosis of transformed cells expressing a KIT W557_K558del/T670I double mutation in culture (PMID: 17699867). 17699867
KIT W557_K558del KIT T670I Advanced Solid Tumor resistant Regorafenib Preclinical Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT T670I demonstrated resistance to treatment with Stivarga (regorafenib) in culture (PMID: 25239608). 25239608
KIT P577_D579del thymic carcinoma predicted - sensitive Sorafenib Case Reports/Case Series Actionable In a clinical case report, a patient with advanced thymic carcinoma harboring KIT P577_D579del demonstrated response to treatment with Nexavar (sorafenib), with a decrease in tumor size (PMID: 20970876). 20970876
KIT N505I melanoma sensitive Sorafenib Preclinical Actionable In a preclinical study, KIT N505I induced phosphorylation of KIT, ERK, and AKT, and was inhibited by Nexavar (sorafenib) in cell culture of melanocytes, demonstrating sensitivity of N505I to sorafenib (PMID: 24317392). 24317392
KIT N505I melanoma predicted - sensitive Imatinib Preclinical Actionable In a preclinical study, Gleevec (imatinib) decreased phosphorylation of KIT, AKT, and ERK in melanocytes expressing KIT N505I in culture (PMID: 24317392). 24317392
KIT over exp seminoma sensitive Imatinib Case Reports/Case Series Actionable In a clinical case study, Gleevec (imatinib) in conjunction with third-line chemotherapy resulted in a complete response in a patient with stage IV chemoresistant pure seminoma with KIT overexpression (PMID: 18751412). 18751412
KIT over exp Advanced Solid Tumor sensitive Derazantinib Preclinical - Cell culture Actionable In a preclinical study, Derazantinib (ARQ 087) inhibited growth of transformed cells overexpressing Kit in culture (PMID: 27627808). 27627808
KIT V559A gastrointestinal stromal tumor predicted - resistant Imatinib Case Reports/Case Series Actionable In a clinical study, KIT V559A was identified as a secondary mutation in a patient with gastrointestinal stromal tumor who developed resistance to Gleevec (imatinib) (PMID: 18488160). 18488160
KIT V559A Advanced Solid Tumor sensitive Axitinib Preclinical - Cell culture Actionable In a preclinical study, Inlyta (axitinib) inhibited KIT phosphorylation and proliferation of transformed cells expressing KIT V559A in culture (PMID: 31205508). 31205508
KIT V559A melanoma predicted - sensitive Imatinib Case Reports/Case Series Actionable In a clinical case study, Gleevec (imatinib) treatment in a patient with metastatic melanoma resulted in regression of the lung metastasis, which harbored KIT V559A; however, neither the primary tumor or lymph node metastasis responded, which had wild-type KIT (PMID: 19812602). 19812602
KIT V559A melanoma sensitive Nilotinib Case Reports/Case Series Actionable In a Phase II trial, Tasigna (nilotinib) resulted in an overall response rate of 26.2% (11/41), including a melanoma patient harboring KIT V559A demonstrating a partial response and progression-free survival of 19.4 months and overall survival of 32.9 months (PMID: 28327988). 28327988
KIT M541L chronic leukemia sensitive Imatinib Phase I Actionable In Phase I trials, KIT M541L has been associated with response to Gleevec (imatinib) in chronic eosinophilic leukemia, NOS (PMID: 25015329) and mastocytosis (PMID: 18795925). 25015329 18795925
KIT D820A KIT V560D gastrointestinal stromal tumor resistant Imatinib Preclinical Actionable In a preclinical study, a gastrointestinal stromal tumor cell line harboring KIT V560D and KIT D820A demonstrated resistance to Gleevec (imatinib) in culture (PMID: 16954519). 16954519
KIT D820A KIT V560D gastrointestinal stromal tumor resistant Imatinib Case Reports/Case Series Actionable In a clinical study, KIT D820A was identified as a secondary mutation in a patient with gastrointestinal stromal tumor harboring a primary KIT V560D mutation, who developed resistance to Gleevec (imatinib mesylate) (PMID: 16954519). 16954519
KIT D820A KIT V560D gastrointestinal stromal tumor resistant Sunitinib Preclinical Actionable In a preclinical study, a gastrointestinal stromal tumor cell line harboring KIT V560D and KIT D820A demonstrated resistance to Sutent (sunitinib) in culture (PMID: 18955458). 18955458
KIT V560D Advanced Solid Tumor sensitive Regorafenib Preclinical Actionable In a preclinical study, transformed cells expressing KIT V560D demonstrated sensitivity to treatment with Stivarga (regorafineb) in culture, resulting in reduced cell viability (PMID: 25239608). 25239608
KIT V560D melanoma sensitive Nilotinib Phase II Actionable In a Phase II trial, Tasigna (nilotinib) resulted in an overall response rate of 26.2% (11/41) including a melanoma patient harboring KIT V560D demonstrating a partial response and progression free survival of 8.6 months and overall survival of 23.5 months (PMID: 28327988). 28327988
KIT V560D Advanced Solid Tumor sensitive Motesanib Preclinical - Cell culture Actionable In a preclinical study, Motesanib (AMG 706) inhibited KIT phosphorylation and growth of cells expressing KIT V560D in culture (PMID: 20633291). 20633291
KIT V560D Advanced Solid Tumor sensitive Sorafenib Preclinical Actionable In a preclinical study, transformed cells expressing KIT V560D were sensitive to Nexavar (sorafenib) in culture (PMID: 22665524). 22665524
KIT V560D Advanced Solid Tumor sensitive Ponatinib Preclinical Actionable In a preclinical study, transformed cells expressing KIT V560D demonstrated sensitivity to treatment with Iclusig (ponatinib) in culture, resulting in reduced cell viability (PMID: 25239608). 25239608
KIT V560D Advanced Solid Tumor sensitive Sunitinib Preclinical Actionable In a preclinical study, transformed cells expressing KIT V560D demonstrated sensitivity to treatment with Sutent (sunitinib) in culture, resulting in reduced cell viability (PMID: 25239608). 25239608
KIT V560D Advanced Solid Tumor sensitive Dasatinib Preclinical Actionable In a preclinical study, transformed cells expressing KIT V560D were sensitive to Sprycel (dasatinib) in culture (PMID: 16397263). 16397263
KIT V560D Advanced Solid Tumor sensitive Imatinib Preclinical Actionable In a preclinical study, transformed cells expressing KIT V560D demonstrated sensitivity to treatment with Gleevec (imatinib) in culture, resulting in reduced cell viability (PMID: 25239608). 25239608
KIT T670I KIT V560D Advanced Solid Tumor sensitive Motesanib Preclinical - Cell culture Actionable In a preclinical study, Motesanib (AMG 706) inhibited KIT phosphorylation and growth of cells expressing a KIT V560D/T670I double mutation in culture (PMID: 20633291). 20633291
KIT T670I KIT V560D Advanced Solid Tumor resistant Flumatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing KIT V560D and KIT T670I were resistant to Flumatinib in culture (PMID: 24205792). 24205792
KIT C443S mucosal melanoma sensitive Imatinib Case Reports/Case Series Actionable In a clinical case study, a patient with mucosal melanoma harboring KIT C443S demonstrated a substantial response to Gleevec (imatinib) in the first two weeks and then developed progression at 15 weeks (PMID: 25003536). 25003536
KIT wild-type acute myeloid leukemia sensitive BPR1J373 Preclinical - Cell culture Actionable In a preclinical study, an acute myeloid leukemia cell line harboring KIT wild-type was sensitive to BPR1J373 in culture, demonstrating apoptotic induction and inhibition of cell proliferation (PMID: 27512117). 27512117
KIT wild-type megakaryocytic leukemia decreased response Avapritinib Preclinical - Cell culture Actionable In a preclinical study, KIT wild-type megakaryocytic leukemia cells were less sensitive to BLU-285 compared to cells harboring KIT mutations in culture (PMID: 29093181). 29093181
KIT V560_L576del gastrointestinal stromal tumor sensitive Ponatinib Preclinical - Pdx & cell culture Actionable In a preclinical study, a patient derived GIST cell line harboring KIT V560_L576del demonstrated sensitivity to Iclusig (ponatinib) in both culture and PDX models, resulting in phosphorylation inhibition of Akt, Kit, and Erk (PMID: 25239608). 25239608
KIT V560_L576del gastrointestinal stromal tumor sensitive Imatinib Preclinical - Pdx & cell culture Actionable In a preclinical study, a patient derived GIST cell line harboring KIT V560_L576del demonstrated sensitivity to Gleevec (imatinib) in both culture and PDX models, resulting in phosphorylation inhibition of Akt, Kit, and Erk (PMID: 25239608). 25239608
KIT V560_Y578del gastrointestinal stromal tumor sensitive BGJ398 + Imatinib Preclinical - Cell culture Actionable In a preclinical study, BGJ398 and Gleevec (imatinib mesylate) combination treatment demonstrated enhanced antiproliferative activity in gastrointestinal stromal tumor cells harboring KIT V560_Y578del in culture (PMID: 25673643). 25673643
KIT V560_Y578del gastrointestinal stromal tumor sensitive Sunitinib Preclinical - Cell culture Actionable In a preclinical study, Sutent (sunitinib) inhibited proliferation of a gastrointestinal stromal tumor cell line harboring KIT V560_Y578del in culture (PMID: 31205508). 31205508
KIT V560_Y578del gastrointestinal stromal tumor sensitive Axitinib Preclinical - Cell line xenograft Actionable In a preclinical study, Inlyta (axitinib) inhibited KIT phosphorylation and downstream signaling, reduced proliferation and induced cell-cycle arrest in a gastrointestinal stromal tumor cell line harboring KIT V560_Y578del in culture, and inhibited tumor growth in xenograft models (PMID: 31205508). 31205508
KIT V560_Y578del gastrointestinal stromal tumor sensitive Ponatinib Preclinical - Patient cell culture Actionable In a preclinical study, a patient-derived gastrointestinal stromal tumor (GIST) cell line harboring KIT V560_Y578del demonstrated sensitivity to Iclusig (ponatinib) in culture (PMID: 25239608). 25239608
KIT V560_Y578del gastrointestinal stromal tumor sensitive Imatinib Preclinical Actionable In a preclinical study, a patient derived GIST cell line harboring KIT V560_Y578del demonstrated sensitivity to Gleevec (imatinib) in culture (PMID: 25239608). 25239608
KIT V560_Y578del KIT A829P gastrointestinal stromal tumor decreased response Sunitinib Preclinical Actionable In a preclinical study, a patient derived GIST cell line co-harboring KIT V560_Y578del and KIT A829P demonstrated a decreased response to treatment with Sutent (sunitinib) (PMID: 25239608). 25239608
KIT V560_Y578del KIT T670I gastrointestinal stromal tumor sensitive Sunitinib Preclinical - Cell culture Actionable In a preclinical study, Sutent (sunitinib) inhibited proliferation of a gastrointestinal stromal tumor cell line harboring KIT V560_Y578del in culture (PMID: 31205508). 31205508
KIT V560_Y578del KIT T670I gastrointestinal stromal tumor sensitive Sunitinib Preclinical - Cell culture Actionable In a preclinical study, a patient-derived gastrointestinal stromal tumor (GIST) cell line co-harboring KIT V560_Y578del and KIT T670I demonstrated sensitivity to treatment with Sutent (sunitinib) (PMID: 25239608). 25239608
KIT V560_Y578del KIT T670I gastrointestinal stromal tumor sensitive Axitinib Preclinical - Cell line xenograft Actionable In a preclinical study, Inlyta (axitinib) inhibited KIT phosphorylation and downstream signaling, reduced proliferation, and induced cell-cycle arrest in a gastrointestinal stromal tumor cell line harboring KIT V560_Y578del and KIT T670I in culture, and inhibited tumor growth in xenograft models (PMID: 31205508). 31205508
KIT V560_Y578del KIT T670I gastrointestinal stromal tumor sensitive Ponatinib Preclinical Actionable In a preclinical study, a patient derived GIST cell line co-harboring KIT V560_Y578del and KIT T670I demonstrated sensitivity to treatment with Iclusig (ponatinib) (PMID: 25239608). 25239608
RUNX1-RUNX1T1 KIT mut acute myeloid leukemia not applicable N/A Clinical Study Prognostic In clinical analyses, coincident KIT mutations were associated with higher relapse rate and decreased overall survival in acute myeloid leukemia patients with RUNX1-RUNX1T1 fusions (PMID: 18648004, PMID: 16384925, PMID: 25111512). 25111512 16384925 18648004
KIT mutant gastrointestinal stromal tumor sensitive HQP1351 Preclinical - Cell line xenograft Actionable In a preclinical study, HQP1351 demonstrated greater tumor inhibition compared to Iclusig (ponatinib) in cell line xenograft models of gastrointestinal stromal tumor harboring secondary KIT mutations (Cancer Res 2018;78(13 Suppl):Abstract nr 1979). detail...
KIT mutant gastrointestinal stromal tumor sensitive BGJ398 + Imatinib Preclinical - Pdx Actionable In a preclinical study, BGJ398 and Gleevec (imatinib mesylate) combination treatment demonstrated enhanced antitumor activity in patient derived xenograft models of gastrointestinal stromal tumor harboring KIT mutations (PMID: 25673643). 25673643
KIT mutant gastrointestinal stromal tumor predicted - sensitive DCC-2618 Phase I Actionable In a Phase I trial, DCC-2618 demonstrated preliminary safety and efficacy in patients with advanced solid tumors, including KIT-mutant gastrointestinal stromal tumor (GIST), with 1 patient harboring KIT exon 11 and 17 mutations demonstrating a partial response, and 7/7 KIT-mutant GIST patients demonstrating a partial metabolic response (EORTC-NCI-AACR 2016, Abs 7LBA). detail...
KIT mutant melanoma sensitive Nilotinib Phase II Actionable In a Phase II trial, Tasigna (nilotinib) treatment in patients with melanoma harboring KIT mutations resulted in an overall response rate of 26.2% (11/42), which included 11 patients with a partial response, a median duration of response of 7.1 months, and an overall survival of 18 months (PMID: 28327988; NCT01028222). 28327988
KIT mutant melanoma sensitive Nilotinib Phase II Actionable In a Phase II trial, Tasigna (nilotinib) treatment resulted in complete response in 4% (1/25), durable partial response in 16% (4/25), and stable disease in 56% (14/25) of melanoma patients harboring KIT mutations (PMID: 28843487; NCT01168050). 28843487
KIT mutant gastrointestinal stromal tumor not applicable N/A Clinical Study Diagnostic KIT mutations are used in the diagnosis of gastrointestinal stromal tumors (PMID: 25193432, PMID: 26276366, PMID: 25729899). 25193432 26276366 25729899
KIT mutant gastrointestinal stromal tumor predicted - sensitive Avapritinib Phase I Actionable In a Phase I (NAVIGATOR) trial, Avapritinib (BLU-285) treatment resulted in an objective response rate of 13% (7/52, 7 partial responses) and a disease control rate of 63% (33/52) in patients with KIT-mutant gastrointestinal stromal tumor (The CTOS 2018 Annual Meeting, Nov 14-17, Rome Italy, Paper 012 3027631; NCT02508532). detail...
KIT P551_E554del Advanced Solid Tumor sensitive Ponatinib Preclinical Actionable In a preclinical study, transformed cells expressing KIT P551_E554del demonstrated sensitivity to treatment with Iclusig (ponatinib) in culture, resulting in reduced cell viability (PMID: 25239608). 25239608
KIT P551_E554del Advanced Solid Tumor resistant Regorafenib Preclinical Actionable In a preclinical study, transformed cells expressing KIT P551_E554del were resistant to treatment with Stivarga (regorafenib) in culture (PMID: 25239608). 25239608
KIT P551_E554del Advanced Solid Tumor resistant Imatinib Preclinical Actionable In a preclinical study, transformed cells expressing KIT P551_E554del were resistant to treatment with Gleevec (imatinib) in culture (PMID: 25239608). 25239608
KIT P551_E554del Advanced Solid Tumor resistant Sunitinib Preclinical Actionable In a preclinical study, transformed cells expressing KIT P551_E554del were resistant to treatment with Sutent (sunitinib) in culture (PMID: 25239608). 25239608
KIT W557_V559delinsF gastrointestinal stromal tumor sensitive Avapritinib Preclinical - Pdx Actionable In a preclinical study, BLU-285 treatment resulted in tumor regression in patient-derived xenograft models of gastrointestinal stromal tumor harboring KIT W557_V559delinsF (PMID: 29093181). 29093181
KIT K642E gastrointestinal stromal tumor sensitive Ponatinib Preclinical Actionable In a preclinical study, a patient derived GIST cell line harboring KIT K642E demonstrated sensitivity to Iclusig (ponatinib) in culture (PMID: 25239608). 25239608
KIT K642E gastrointestinal stromal tumor sensitive Sunitinib Preclinical - Patient cell culture Actionable In a preclinical study, Sutent (sunitinib) inhibited proliferation of a gastrointestinal stromal tumor (GIST) cell line and primary GIST patient-derived cells harboring KIT K642E in culture (PMID: 31205508). 31205508
KIT K642E gastrointestinal stromal tumor sensitive Axitinib Preclinical - Patient cell culture Actionable In a preclinical study, Inlyta (axitinib) inhibited phosphorylation of KIT and downstream signaling, reduced proliferation, and induced cell-cycle arrest in a cultured gastrointestinal stromal tumor (GIST) cell line harboring KIT K642E, and inhibited proliferation of primary GIST cells harboring KIT K642E in culture (PMID: 31205508). 31205508
KIT K642E vulvar melanoma predicted - sensitive Imatinib Case Reports/Case Series Actionable In a clinical case study, Gleevec (imatinib) treatment resulted in partial response in a patient with recurrent vulval melanoma harboring KIT K642E, with reduction of tumor mass by 35% at 12 weeks (PMID: 20372153). 20372153
KIT K642E gastrointestinal stromal tumor sensitive BGJ398 + Imatinib Preclinical - Cell culture Actionable In a preclinical study, BGJ398 and Gleevec (imatinib mesylate) combination treatment demonstrated enhanced antiproliferative activity in gastrointestinal stromal tumor cells harboring KIT K642E in culture (PMID: 25673643). 25673643
KIT K642E gastrointestinal stromal tumor sensitive Regorafenib Preclinical - Cell culture Actionable In a preclinical study, Stivarga (regorafenib) inhibited proliferation of gastrointestinal stromal tumor cells harboring KIT K642E in culture (PMID: 21170960). 21170960
KIT K642E melanoma sensitive Nilotinib Phase II Actionable In a Phase II trial, Tasigna (nilotinib) resulted in an overall response rate of 26.2% (11/41) including a melanoma patient harboring KIT K642E demonstrating a partial response and a progression free survival of 5.8 months and overall survival of 18.6 months (PMID: 28327988). 28327988
KIT D816H Advanced Solid Tumor predicted - sensitive Flumatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT D816H were more sensitive to treatment with Flumatinib in culture compared to Gleevec (imatinib) (PMID: 24205792). 24205792
KIT D816H Advanced Solid Tumor predicted - sensitive Sunitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT D816H were more sensitive to treatment with Sutent (sunitinib) in culture compared to Gleevec (imatinib) (PMID: 24205792). 24205792
KIT D816H Advanced Solid Tumor resistant Regorafenib Preclinical Actionable In a preclinical study, KIT D816H demonstrated resistance to Stivarga (regorafenib) in an in vitro assay, and conferred secondary resistance to Stivarga (regorafenib) in transformed cells expressing other KIT mutations (PMID: 25239608). 25239608
KIT D816H Advanced Solid Tumor sensitive Ponatinib Preclinical Actionable In a preclinical study, cells expressing KIT D816H demonstrated sensitivity to Iclusig (ponatinib) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT D816H Advanced Solid Tumor predicted - sensitive AZD3229 Preclinical - Cell line xenograft Actionable In a preclinical study, AZD3229 inhibited Kit signaling, resulted in tumor regression in cell line xenograft models of transformed cells expressing KIT D816H (Proceedings of the American Association for Cancer Research, Vol 60, Mar 2019, Abstract #1328). detail...
KIT I571_D579dup Advanced Solid Tumor predicted - resistant Imatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT I571_D579dup (KIT D579_H580insIDPTQLPYD) were moderately resistant to Gleevec (imatinib) in culture (PMID: 24205792). 24205792
KIT I571_D579dup Advanced Solid Tumor predicted - resistant Flumatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT I571_D579dup (KIT D579_H580insIDPTQLPYD) were moderately resistant to Flumatinib in culture (PMID: 24205792). 24205792
KIT I571_D579dup Advanced Solid Tumor predicted - resistant Sunitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT I571_D579dup (KIT D579_H580insIDPTQLPYD) were moderately resistant to Sutent (sunitinib) in culture (PMID: 24205792). 24205792
KIT T670I gastrointestinal stromal tumor predicted - sensitive Imatinib Case Reports/Case Series Actionable In a clinical case report, a patient with a gastrointestinal stromal tumor developed disease progression while being treated with Gleevec (imatinib), demonstrating a KIT T670I mutation in the progressive lesion (PMID: 15236194). 15236194
KIT T670I melanoma sensitive Sunitinib Preclinical Actionable In a preclinical study, Sutent (sunitinib) demonstrated efficacy by inhibiting proliferation of cultured melanoma cells expressing KIT T670I (PMID: 23582185, PMID: 25594040). 23582185 25594040
KIT T670I melanoma resistant Dasatinib Preclinical Actionable In a preclinical study, melanoma cells expressing KIT T670I demonstrated resistance to treatment with Sprycel (dasatinib) (PMID: 23582185, PMID: 25594040). 23582185 25594040
KIT T670I Advanced Solid Tumor sensitive Ponatinib Preclinical Actionable In a preclinical study, cells expressing KIT T670I demonstrated sensitivity to Iclusig (ponatinib) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT T670I Advanced Solid Tumor sensitive Axitinib Preclinical - Cell culture Actionable In a preclinical study, Inlyta (axitinib) inhibited KIT phosphorylation and proliferation of transformed cells expressing KIT T670I in culture, however, with decreased potency compared to its potency against other KIT variants (PMID: 31205508). 31205508
KIT T670I melanoma resistant Nilotinib Preclinical Actionable In a preclinical study, melanoma cells expressing KIT T670I demonstrated resistance to treatment with Tasigna (nilotinib) (PMID: 23582185, PMID: 25594040). 23582185 25594040
KIT T670I melanoma resistant Imatinib Preclinical Actionable In a preclinical study, melanoma cells expressing KIT T670I demonstrated resistance to treatment with Gleevec (imatinib mesylate) (PMID: 23582185, PMID: 25594040). 23582185 25594040
KIT T670I Advanced Solid Tumor sensitive Sunitinib Preclinical - Cell culture Actionable In a preclinical study, Sutent (sunitinib) inhibited proliferation of transformed cells expressing KIT T670I in culture (PMID: 31205508). 31205508
KIT A829P Advanced Solid Tumor sensitive Ponatinib Preclinical Actionable In a preclinical study, cells expressing KIT A829P demonstrated sensitivity to Iclusig (ponatinib) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT A829P melanoma sensitive Nilotinib Preclinical Actionable In a preclinical study, Tasigna (nilotinib) demonstrated efficacy by inhibiting proliferation of cultured melanoma cells expressing KIT A829P (PMID: 23582185, PMID: 25594040). 23582185 25594040
KIT A829P Advanced Solid Tumor sensitive Axitinib Preclinical - Cell culture Actionable In a preclinical study, Inlyta (axitinib) inhibited KIT phosphorylation and proliferation of transformed cells expressing KIT A829P in culture, however, with decreased potency compared to its potency against other KIT variants (PMID: 31205508). 31205508
KIT A829P melanoma sensitive Dasatinib Preclinical Actionable In a preclinical study, Sprycel (dasatinib) demonstrated efficacy by inhibiting proliferation of cultured melanoma cells expressing KIT A829P (PMID: 23582185, PMID: 25594040). 23582185 25594040
KIT A829P melanoma resistant Sunitinib Preclinical Actionable In a preclinical study, melanoma cells expressing KIT A829P demonstrated resistance to treatment with Sutent (sunitinib) (PMID: 23582185, PMID: 25594040). 23582185 25594040
KIT A829P melanoma resistant Imatinib Preclinical Actionable In a preclinical study, melanoma cells expressing KIT A829P demonstrated resistance to treatment with Gleevec (imatinib mesylate) (PMID: 23582185, PMID: 25594040). 23582185 25594040
KIT V560G Advanced Solid Tumor sensitive Nilotinib Preclinical Actionable In a preclinical study, transformed cells expressing KIT V560G demonstrated inhibition of cell proliferation and tumor regression both in culture and in vivo when treated with Tasigna (nilotinib) (PMID: 20442311). 20442311
KIT V560G mast-cell leukemia sensitive Avapritinib Preclinical - Cell culture Actionable In a preclinical study, BLU-285 inhibited Kit phosphorylation and proliferation of mast cell leukemia cells harboring KIT V560G in culture (PMID: 29093181). 29093181
KIT V560G Advanced Solid Tumor sensitive Ponatinib Preclinical Actionable In a preclinical study, cells expressing KIT V560G demonstrated sensitivity to Iclusig (ponatinib) in an in vitro kinase assay (PMID: 25239608). 25239608
Clinical Trial Phase Therapies Title Recruitment Status