Molecular Profile Detail

Profile Name PDGFRA H845Y
Gene Variant Detail

PDGFRA H845Y (gain of function)

Relevant Treatment Approaches PDGFR Inhibitor (Pan) PDGFR-alpha Inhibitor

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
PDGFRA L221F gastrointestinal stromal tumor sensitive PDGFR Inhibitor (Pan) Imatinib Phase I Actionable In a Phase I retrospective study, treatment with Gleevec (imatinib) demonstrated a prolonged response in a patient with a gastrointestinal stromal tumor harboring a PDGFRA L221F mutation (PMID: 22718859). 22718859
PDGFRA V561D Advanced Solid Tumor sensitive PDGFR Inhibitor (Pan) Imatinib Preclinical Actionable In a preclinical study, cells expressing PDGFRA V561D demonstrated sensitivity to Gleevec (imatinib) in cell culture (PMID: 15928335). 15928335
PDGFRA V561D Advanced Solid Tumor sensitive PDGFR-alpha Inhibitor Avapritinib Preclinical - Cell culture Actionable In a preclinical study, BLU-285 inhibited Kit phosphorylation in transformed cells overexpressing PDGFRA V561D in culture (PMID: 29093181). 29093181
PDGFRA D842V PDGFRA V561D Advanced Solid Tumor resistant PDGFR Inhibitor (Pan) Sunitinib Preclinical - Cell culture Actionable In a preclinical study, PDGFRA D842V conferred resistance to inhibition of PDGFRA phosphorylation by Sutent (sunitinib) in cells expressing PDGFRA V561D in culture (PMID: 18955458). 18955458
PDGFRA V561_I562insER Advanced Solid Tumor sensitive PDGFR Inhibitor (Pan) Imatinib Preclinical - Cell culture Actionable In a preclinical study, Gleevec (imatinib) inhibited Pdgfra phosphorylation in transformed cells over expressing PDGFRA V561_I562insER in culture (PMID: 21224473). 21224473
PDGFRA P577S Advanced Solid Tumor sensitive PDGFR Inhibitor (Pan) Imatinib Preclinical Actionable In a preclinical study, Gleevec (imatinib) inhibited Pdgfra phosphorylation and decreased proliferation in cells expressing PDGFRA P577S in culture (PMID: 24132921). 24132921
PDGFRA P577S Advanced Solid Tumor sensitive PDGFR Inhibitor (Pan) Crenolanib Preclinical Actionable In a preclinical study, crenolanib inhibited Pdgfra phosphorylation and decreased proliferation in cells expressing PDGFRA P577S in culture (PMID: 24132921). 24132921
CDKN2A mut MET del exon14 PDGFRA mut SMAD4 Q249H melanoma sensitive PDGFR Inhibitor (Pan) Imatinib + Carboplatin + Paclitaxel Clinical Study Actionable In a clinical study, a melanoma patient harboring a PDGFRA mutation, CDKN2A mutation, MET exon 14 splice site mutation, and SMAD4 Q249H demonstrated a 21 month overall survival when treated with a combination of Gleevec (imatinib), Paraplatin (carboplatin), and Taxol (paclitaxel) (PMID: 28514312). 28514312
PDGFRA mutant gastrointestinal stromal tumor not applicable N/A Clinical Study Diagnostic PDGFRA mutations are used in the diagnosis of gastrointestinal stromal tumors (PMID: 26276366, PMID: 25729899). 25729899 26276366
PDGFRA D842V Advanced Solid Tumor sensitive PDGFR Inhibitor (Pan) Crenolanib Preclinical - Cell culture Actionable In a preclinical study, Crenolanib inhibited Pdgfra phosphorylation and proliferation of transformed cells expressing PDGFRA D842V in culture (PMID: 22745105). 22745105
PDGFRA D842V Advanced Solid Tumor sensitive PDGFR-alpha Inhibitor Avapritinib Preclinical - Cell culture Actionable In a preclinical study, BLU-285 inhibited Kit phosphorylation in transformed cells overexpressing PDGFRA D842V in culture (PMID: 29093181). 29093181
PDGFRA D842V gastrointestinal stromal tumor predicted - sensitive PDGFR Inhibitor (Pan) Regorafenib Clinical Study Actionable In a clinical study, Stivarga (regorafenib) treatment resulted in partial response in 11% (2/18) of patients and stable disease in 39% (7/18) of gastrointestinal stromal tumor patients, including prolonged stable disease for 12 months in a patient harboring PDGFRA D842V (PMID: 25905001). 25905001
PDGFRA D842V gastrointestinal stromal tumor sensitive PDGFR-alpha Inhibitor Avapritinib Phase I Actionable In a Phase I trial, BLU-285 treatment resulted in partial response lasted for more than 15 cycles of treatment, and sustained reduction of plasma PDGFRA D842V in a patient with gastrointestinal stromal tumor harboring PDGFRA D842V, whose disease had progressed on previous Gleevec (imatinib mesylate), Sprycel (dasatinib), and Crenolanib treatment (PMID: 29093181; NCT02508532). 29093181
PDGFRA D842V gastrointestinal stromal tumor predicted - sensitive PDGFR Inhibitor (Pan) Dasatinib Phase 0 Actionable In a clinical trial, Sprycel (dasatinib) treatment resulted in a partial response in 25% (12/48) of patients with Gleevec (imatinib)-resistant gastrointestinal stromal tumor, with decreased tumor size in 2 of those patients, 1 of which harbored PDGFRA D842V (PMID: 29710216). 29710216
PDGFRA D842V Advanced Solid Tumor resistant PDGFR Inhibitor (Pan) Sunitinib Preclinical - Cell culture Actionable In a preclinical study, cells expressing PDGFRA D842V demonstrated resistance to inhibition of PDGFRA phosphorylation by Sutent (sunitinib) in culture (PMID: 18955458). 18955458
PDGFRA D842V Advanced Solid Tumor resistant PDGFR Inhibitor (Pan) Imatinib Preclinical Actionable In a preclinical study, expression of PDGFRA D842V conferred resistance to Gleevec (imatinib) in cell culture (PMID: 15928335). 15928335
PDGFRA D842V gastrointestinal stromal tumor sensitive PDGFR Inhibitor (Pan) Crenolanib Phase Ib/II Actionable In a Phase I/II trial, treatment with Crenolanib (CP-868596) resulted in a clinical benefit rate of 31% (5/16) in gastronintestinal stromal tumor patients harboring PDGFRA D842V, with partial response in 2/16 and stable disease in 3/16 patients (J Clin Oncol 34, 2016 (suppl; abstr 11010)). detail...
PDGFRA D842V Advanced Solid Tumor resistant PDGFR Inhibitor (Pan) Nilotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing PDGFRA D842V demonstrated resistance to growth inhibition by Tasigna (nilotinib) in culture (PMID: 18794084). 18794084
PDGFRA V658A Advanced Solid Tumor sensitive PDGFR Inhibitor (Pan) Crenolanib Preclinical Actionable In a preclinical study, crenolanib inhibited Pdgfra phosphorylation and decreased proliferation in cells expressing PDGFRA V658A in culture (PMID: 24132921). 24132921
PDGFRA V658A Advanced Solid Tumor sensitive PDGFR Inhibitor (Pan) Imatinib Preclinical Actionable In a preclinical study, crenolanib inhibited Pdgfra phosphorylation and decreased proliferation in transformed human cells expressing PDGFRA V658A in culture (PMID: 24132921). 24132921
PDGFRA H650Q leukemia sensitive PDGFR Inhibitor (Pan) Imatinib Preclinical Actionable In a preclinical study, mice injected with transformed cells harboring PDGFRA H650Q developed leukemia-like disease that is sensitive to Gleevec (imatinib) (PMID: 21224473). 21224473
PDGFRA D842_I843delinsIM Advanced Solid Tumor resistant PDGFR Inhibitor (Pan) Imatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells over expressing PDGFRA D842_I843delinsIM were resistant to inhibition of Pdgfra phosphorylation by Gleevec (imatinib) in culture (PMID: 21224473). 21224473
PDGFRA D842X gastrointestinal stromal tumor sensitive PDGFR-alpha Inhibitor Avapritinib Phase I Actionable In a Phase I (NAVIGATOR) trial, Avapritinib (BLU-285) treatment resulted in an objective response rate of 70% (26/37, 2 complete responses, 24 partial responses) and a disease control rate of 97% (36/37) in patients with gastrointestinal stromal tumor harboring PDGFRA D842 mutations (The CTOS 2018 Annual Meeting, Nov 14-17, Rome Italy, Paper 012 3027631; NCT02508532). detail...
PDGFRA D842X gastrointestinal stromal tumor sensitive PDGFR-alpha Inhibitor Avapritinib Phase I Actionable In a Phase I trial, BLU-285 demonstrated preliminary antitumor activity in gastrointestinal stromal tumor patients harboring PDGFRA D842 mutations, with partial responses in 50% (6/12) and stable disease in 50% (6/12) of patients (EORTC-NCI-AACR 2016, Abs 6LBA). detail...
PDGFRA act mut gastrointestinal stromal tumor not applicable N/A Guideline Diagnostic PDGFRA activating mutations aid the diagnosis of gastrointestinal stromal tumor (NCCN.org). detail...
PDGFRA act mut pancreatic cancer predicted - sensitive Vistusertib Phase I Actionable In a Phase I trial, Vistusertib (AZD2014) demonstrated safety and preliminary efficacy in patients with advanced solid tumors, including a patient with pancreatic cancer harboring a PDGFRA activating mutation (PMID: 25805799). 25805799
PDGFRA rearrange myelodysplastic/myeloproliferative neoplasm sensitive PDGFR Inhibitor (Pan) Imatinib FDA approved Actionable Gleevec (imatinib) is FDA approved for myelodysplastic/myeloproliferative cancers that are associated with PDGFR rearrangements (FDA.gov). detail...
PDGFRA H845Y Advanced Solid Tumor sensitive PDGFR Inhibitor (Pan) Crenolanib Preclinical Actionable In a preclinical study, crenolanib inhibited Pdgfra phosphorylation in cells expressing PDGFRA H845Y in culture (PMID: 24132921). 24132921
PDGFRA H845Y Advanced Solid Tumor sensitive PDGFR Inhibitor (Pan) Imatinib Preclinical Actionable In a preclinical study, Gleevec (imatinib) inhibited Pdgfra phosphorylation in cells expressing PDGFRA H845Y in culture (PMID: 24132921). 24132921
PDGFRA Y849S Advanced Solid Tumor sensitive PDGFR Inhibitor (Pan) Imatinib Preclinical - Cell culture Actionable In a preclinical study, Gleevec (imatinib) inhibited Pdgfra phosphorylation and cell proliferation in transformed cells over expressing PDGFRA Y849S in culture (PMID: 21224473). 21224473
PDGFRA Y849S myeloid leukemia sensitive PDGFR Inhibitor (Pan) Imatinib Preclinical - Cell culture Actionable In a preclinical study, Gleevec (imatinib) inhibited growth of transformed mouse myeloid cells over expressing PDGFRA Y849S in culture (PMID: 21224473). 21224473
PDGFRA D846Y Advanced Solid Tumor sensitive PDGFR Inhibitor (Pan) Imatinib Preclinical - Cell culture Actionable In a preclinical study, Gleevec (imatinib) inhibited Pdgfra phosphorylation and cell proliferation in transformed cells over expressing PDGFRA D846Y in culture (PMID: 21224473). 21224473
PDGFRA N659K Advanced Solid Tumor sensitive PDGFR Inhibitor (Pan) Crenolanib Preclinical Actionable In a preclinical study, crenolanib decreased Pdgfra phosphorylation in cells expressing PDGFRA N659K in culture (PMID: 22745105). 22745105
PDGFRA N659K Advanced Solid Tumor sensitive PDGFR Inhibitor (Pan) Imatinib Preclinical Actionable In a preclinical study, Gleevec (imatinib) decreased Pdgfra phosphorylation in cells expressing PDGFRA N659K in culture (PMID: 22745105). 22745105
KIT amp PDGFRA amp glioblastoma multiforme sensitive PDGFR-alpha Inhibitor 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...
PDGFRA amp lung small cell carcinoma sensitive PDGFR-alpha Inhibitor Ponatinib Preclinical Actionable In a preclinical study, Iclusig (ponatinib) inhibited growth of lung squamous cell cancer cells with PDGFRA amplification in culture (PMID: 22328973). 22328973
PDGFRA amp lung squamous cell carcinoma sensitive PDGFR Inhibitor (Pan) Dasatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Sprycel (dasatinib) inhibited growth of a lung squamous cell cancer (SCC) cell line with amplification of PDGFRA in culture, and inhibited tumor growth in PDGFRA-amplified lung SCC xenograft models (PMID: 22328973). 22328973
PDGFRA amp non-small cell lung carcinoma sensitive PDGFR Inhibitor (Pan) Sunitinib Preclinical Actionable In a preclinical study, Sutent (sunitinib) decreased cell proliferation and inhibited downstream signaling in a NSCLC cell line harboring a PDGFRA amplification (PMID: 19366796). 19366796
PDGFRA amp malignant peripheral nerve sheath tumor sensitive PDGFR Inhibitor (Pan) Imatinib Preclinical Actionable In a preclinical study, a malignant peripheral nerve sheath tumor cell line harboring a PDGFRA amplification demonstrated cell growth inhibition when treated with Gleevec (imatinib) (PMID: 16357008). 16357008
PDGFRA amp lung squamous cell carcinoma sensitive PDGFR Inhibitor (Pan) Imatinib Preclinical Actionable In a preclinical study, Gleevec (imatinib) inhibited growth of lung squamous cell cancer cells with PDGFRA amplification in culture (PMID: 22328973). 22328973
ROS1 fusion KDR amp KIT amp PDGFRA amp non-small cell lung carcinoma predicted - resistant Crizotinib Clinical Study 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
PDGFRA S566_E571delinsR Advanced Solid Tumor sensitive PDGFR Inhibitor (Pan) Imatinib Preclinical - Cell culture Actionable In a preclinical study, Gleevec (imatinib) inhibited Pdgfra phosphorylation in transformed cells over expressing PDGFRA S566_E571delinsR in culture (PMID: 21224473). 21224473
PDGFRA H845_N848delinsP Advanced Solid Tumor sensitive PDGFR Inhibitor (Pan) Imatinib Preclinical - Cell culture Actionable In a preclinical study, Gleevec (imatinib) inhibited Pdgfra phosphorylation in transformed cells over expressing PDGFRA H845_N848delinsP in culture (PMID: 21224473). 21224473
PDGFRA I843del Advanced Solid Tumor sensitive PDGFR Inhibitor (Pan) Imatinib Preclinical Actionable In a preclinical study, Gleevec (imatinib) decreased phosphorylation of Pdgfra in cell lines expressing PDGFRA I843del mutation in culture (PMID: 14645423). 14645423
KIT A502_Y503dup PDGFRA H687Y gastrointestinal stromal tumor predicted - resistant PDGFR Inhibitor (Pan) Imatinib Clinical Study 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, who developed resistance to Gleevec (imatinib mesylate) (PMID: 18488160). 18488160
PDGFRA N659S myeloid leukemia decreased response PDGFR Inhibitor (Pan) Imatinib Preclinical - Cell culture Actionable In a preclinical study, transformed mouse myeloid cells over expressing PDGFRA N659S demonstrated reduced sensitivity to Gleevec (imatinib) in culture (PMID: 21224473). 21224473
PDGFRA D842Y Advanced Solid Tumor sensitive PDGFR Inhibitor (Pan) Imatinib Preclinical Actionable In a preclinical study, Gleevec (imatinib) inhibited Pdgfra phosphorylation and decreased proliferation in transformed human cells expressing PDGFRA D842Y in culture (PMID: 24132921). 24132921
PDGFRA D842Y Advanced Solid Tumor sensitive PDGFR Inhibitor (Pan) Crenolanib Preclinical Actionable In a preclinical study, Crenolanib inhibited Pdgfra phosphorylation and decreased proliferation in transformed human cells expressing PDGFRA D842Y in culture (PMID: 24132921). 24132921
PDGFRA G853D Advanced Solid Tumor sensitive PDGFR Inhibitor (Pan) Imatinib Preclinical Actionable In a preclinical study, Gleevec (imatinib) inhibited Pdgfra phosphorylation and decreased proliferation in transformed human cells expressing PDGFRA G853D in culture (PMID: 24132921). 24132921
PDGFRA G853D Advanced Solid Tumor sensitive PDGFR Inhibitor (Pan) Crenolanib Preclinical Actionable In a preclinical study, crenolanib inhibited Pdgfra phosphorylation and decreased proliferation in transformed human cells expressing PDGFRA G853D in culture (PMID: 24132921). 24132921
PDGFRA R841K Advanced Solid Tumor sensitive PDGFR Inhibitor (Pan) Imatinib Preclinical Actionable In a preclinical study, Gleevec (imatinib) inhibited Pdgfra phosphorylation and decreased proliferation in cells expressing PDGFRA R841K in culture (PMID: 24132921). 24132921
PDGFRA R841K Advanced Solid Tumor sensitive PDGFR Inhibitor (Pan) Crenolanib Preclinical Actionable In a preclinical study, crenolanib inhibited Pdgfra phosphorylation and decreased proliferation in cells expressing PDGFRA R841K in culture (PMID: 24132921). 24132921
PDGFRA R748G myeloid leukemia sensitive PDGFR Inhibitor (Pan) Imatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Gleevec (imatinib) inhibited growth of transformed mouse myeloid cells over expressing PDGFRA R748G in culture and prolonged survival in xenograft models (PMID: 21224473). 21224473
PDGFRA R841_D842delinsKI Advanced Solid Tumor resistant PDGFR Inhibitor (Pan) Imatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells over expressing PDGFRA R841_D842delinsKI were resistant to inhibition of Pdgfra phosphorylation by Gleevec (imatinib) in culture (PMID: 21224473). 21224473
Clinical Trial Phase Therapies Title Recruitment Status