Molecular Profile Detail

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Profile Name RB1 K240Sfs*22
Gene Variant Detail

RB1 K240Sfs*22 (loss of function - predicted)

Relevant Treatment Approaches HDAC Inhibitor

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
RB1 I101fs RB1 E268* RB1 V654fs RB1 T738_R775del Her2-receptor negative breast cancer predicted - resistant Fulvestrant + Palbociclib Case Reports/Case Series Actionable In a clinical case study, RB1 mutations including E268*, I101fs, T738_R775del, and V654fs were identified in the circulating tumor DNA of a patient with estrogen receptor positive, progesterone receptor positive, and Erbb2 (Her2)-negative, invasive ductal carcinoma at the time of disease progression after 8 months of Ibrance (palbociclib) and Faslodex (fulvestrant) combination treatment (PMID: 29236940). 29236940
RB1 negative breast cancer no benefit SHR6390 Preclinical - Cell culture Actionable In a preclinical study, SHR6390 (dalpiciclib) demonstrated little cytotoxic activity against a RB1-negative breast cancer cell line in culture (PMID: 30724426). 30724426
RB1 inact mut retinoblastoma sensitive Fostamatinib Preclinical Actionable In a preclinical study, retinoblastoma cell lines demonstrated sensitivity to Fostamatinib resulting in cell death (PMID: 22237022). 22237022
RB1 inact mut glioblastoma resistant Palbociclib Preclinical - Cell line xenograft Actionable In a preclinical study, Ibrance (palbociclib) failed to inhibit growth of RB1-deficient glioblastoma cell lines in culture and in intracranial cell line xenograft models (PMID: 20354191). 20354191
RB1 inact mut retinoblastoma sensitive Nutlin-3a Preclinical Actionable In a preclinical study, Nutlin-3a induced p53 pathway signaling in MDMX mouse models with retinoblastoma and 69% (70/102) of the eyes harvested from the mouse models demonstrated complete response or stable disease after 18 weeks of therapy (PMID: 21515735). 21515735
RB1 inact mut retinoblastoma sensitive BAY 61-3606 Preclinical Actionable In a preclinical study, a retinoblastoma cell line was sensitive to BAY 61-3606 in cell culture and in xenograft models, demonstrating increased apoptosis (PMID: 22237022). 22237022
CDKN2A pos RB1 inact mut glioblastoma resistant Palbociclib Preclinical - Patient cell culture Actionable In a preclinical study, patient-derived glioblastoma cells harboring RB1 truncation mutation and expressing Cdkn2a were resistant to Ibrance (palbociclib) in culture (PMID: 22711607). 22711607
RB1 wild-type TP53 mut osteosarcoma sensitive R547 Preclinical Actionable In a preclinical study, R547 inhibited proliferation of osteosarcoma cell lines harboring mutant Tp53 and wild-type Rb1 (PMID: 17121911). 17121911
RB1 wild-type TP53 mut mantle cell lymphoma sensitive R547 Preclinical Actionable In a preclinical study, R547 inhibited proliferation of mantle cell lymphoma cell lines harboring mutant Tp53 and wild-type Rb1 (PMID: 17121911). 17121911
RB1 wild-type TP53 mut breast carcinoma sensitive R547 Preclinical - Cell line xenograft Actionable In a preclinical study, R547 inhibited proliferation of breast carcinoma cell lines harboring mutant Tp53 and wild-type Rb1 in culture and reduced tumor growth in xenograft models (PMID: 17121911). 17121911
RB1 wild-type TP53 mut colon carcinoma sensitive R547 Preclinical Actionable In a preclinical study, R547 inhibited proliferation of colon carcinoma cell lines harboring mutant Tp53 and wild-type Rb1 (PMID: 17121911). 17121911
RB1 wild-type TP53 wild-type breast carcinoma sensitive R547 Preclinical Actionable In a preclinical study, R547 inhibited proliferation of breast carcinoma cell lines harboring wild-type Tp53 and Rb1 (PMID: 17121911). 17121911
RB1 wild-type TP53 wild-type lung carcinoma sensitive R547 Preclinical - Cell line xenograft Actionable In a preclinical study, R547 inhibited proliferation of lung carcinoma cell lines harboring wild-type Tp53 and Rb1 in culture and reduced tumor growth in xenograft models (PMID: 17121911). 17121911
RB1 wild-type TP53 wild-type mantle cell lymphoma sensitive R547 Preclinical Actionable In a preclinical study, R547 inhibited proliferation of mantle cell lymphoma cell lines harboring wild-type Tp53 and Rb1 (PMID: 17121911). 17121911
RB1 wild-type TP53 wild-type melanoma sensitive R547 Preclinical - Cell line xenograft Actionable In a preclinical study, R547 inhibited proliferation of melanoma cell lines harboring wild-type Tp53 and Rb1 in culture and reduced tumor growth in xenograft models (PMID: 17121911). 17121911
RB1 wild-type TP53 wild-type colon carcinoma sensitive R547 Preclinical - Cell line xenograft Actionable In a preclinical study, R547 inhibited proliferation of colon carcinoma cell lines harboring wild-type Tp53 and Rb1 in culture and reduced tumor growth in xenograft models (PMID: 17121911). 17121911
RB1 K240Sfs*22 TP53 R248W Her2-receptor negative breast cancer predicted - resistant Fulvestrant + Palbociclib Case Reports/Case Series Actionable In a clinical case study, RB1 K240Sfs*22 and TP53 R248W were identified in the circulating tumor DNA of a patient with estrogen receptor positive, progesterone receptor positive, and Erbb2 (Her2)-negative, invasive ductal carcinoma at the time of disease progression after 5 months of Ibrance (palbociclib) and Faslodex (fulvestrant) combination treatment (PMID: 29236940). 29236940
RB1 positive prostate cancer no benefit Palbociclib Phase II Actionable In a Phase II trial, addition of Ibrance (palbociclib) to androgen deprivation therapy (ADT) did not improve the rate of PSA less or equal to 4 ng/ml at 28 weeks (80%, 32/40 vs 80%, 16/20, p=0.87), PSA undetectable rate at 28 weeks (43% vs 50%, p=0.5), radiographic response rate (89% vs 89%), or 12-month biochemical progression-free survival (74% vs 69%, p=0.72) in patients with metastatic hormone-sensitive prostate cancer expressing Rb1 as confirmed by IHC (PMID: 33727260; NCT02059213). 33727260
RB1 positive breast cancer predicted - sensitive Paclitaxel + Palbociclib Phase I Actionable In a Phase I trial, alternating sequential treatment with Ibrance (palbociclib) and Taxol (paclitaxel) resulted in a median progression-free survival (mPFS) of 209 days in patients with Rb1-positive breast cancer, with a mPFS of 802 days and a clinical benefit rate of 55.6% (5/9) at the recommended phase II dose (PMID: 30635336; NCT01320592). 30635336
RB1 positive Advanced Solid Tumor sensitive SHR6390 Preclinical - Cell culture Actionable In a preclinical study, SHR6390 (dalpiciclib) inhibited CDK4/6-RB pathway signaling, leading to cell cycle arrest and inhibition of proliferation in a panel of RB1-positive tumor cell lines in culture, and tumor growth inhibition in cell line xenograft models (PMID: 30724426). 30724426
RB1 positive Advanced Solid Tumor predicted - sensitive Ribociclib Phase I Actionable In a Phase I clinical trial, Kisqali (ribociclib) demonstrated safety and preliminary efficacy in patients with RB1-positive solid tumors and lymphomas, resulting in partial responses in 2.3% (3/132) of patients and stable disease in 32.6% (41/132) of patients, including 8 patients demonstrating stable disease for greater than 6 months (PMID: 27542767, PMID: 24795392). detail... 24795392 27542767
RB1 positive colon cancer sensitive SHR6390 Preclinical - Cell line xenograft Actionable In a preclinical study, SHR6390 (dalpiciclib) inhibited CDK4/6-RB pathway activation, leading to growth inhibition in an RB1-positive colon cancer cell line in culture, and tumor regression in a cell line xenograft model (PMID: 30724426). 30724426
RB1 positive glioblastoma predicted - sensitive Palbociclib Preclinical - Cell line xenograft Actionable In a preclinical study, Ibrance (palbociclib) inhibited proliferation of RB1-proficient glioblastoma cell lines in culture and inhibited tumor growth in intracranial cell line xenograft models (PMID: 20354191). 20354191
RB1 positive medulloblastoma sensitive Palbociclib Preclinical - Pdx Actionable In a preclinical study, Ibrance (palbociclib) inhibited Rb1 phosphorylation in tumor tissues and improved survival in patient-derived intracranial xenograft models of medulloblastoma (PMID: 27012813). 27012813
CDKN2A del RB1 pos glioblastoma predicted - sensitive Ribociclib Phase 0 Actionable In a Phase 0 trial, Kisqali (ribociclib) demonstrated good CNS penetration and inhibited Rb1 phosphorylation and tumor cell proliferation, resulted in a median progression-free survival of 9.7 weeks and a median overall survival of 7.8 months in patients (n=6) with recurrent glioblastoma with intact Rb1 expression and harboring deletion of CDKN2A or amplification of CDK4 or CDK6 (PMID: 31285369; NCT02933736). 31285369
BRAF V600E/K CDKN2A loss RB1 pos melanoma predicted - sensitive Palbociclib + Vemurafenib Phase Ib/II Actionable In a phase I/II trial, Ibrance (palbociclib) plus Zelboraf (vemurafenib) was safe and resulted in an overall response rate (ORR) of 26.7% (4/15), disease control rate (DCR) of 80% (12/15), and progression-free survival (PFS) of 2.8 mo in metastatic melanoma patients with prior BRAF inhibitor treatment and BRAF V600E/K, CDKN2A loss, and RB1 expression, and an ORR of 27.8% (5/18), DCR of 83.3% (10/18) and 2.8 mo PFS when combined with pts without prior BRAF inhibitor treatment (PMID: 33947696; NCT02202200). 33947696
RB1 H483Y Her2-receptor negative breast cancer predicted - resistant Letrozole + Ribociclib Case Reports/Case Series Actionable In a clinical case study, RB1 H48Y was identified in the circulating tumor DNA of a patient with estrogen receptor positive, progesterone receptor positive, and Erbb2 (Her2)-negative, invasive ductal carcinoma at the time of disease progression after 13 months of Kisqali (ribociclib) and Femara (letrozole) combination treatment (PMID: 29236940). 29236940
ALK rearrange RB1 C706F TP53 loss lung small cell carcinoma predicted - resistant Lorlatinib Case Reports/Case Series Actionable In a clinical case study, RB1 C706F and loss of exons 1-11 in TP53 were identified in the pericardium infiltrating small cell lung cancer that developed while on Lorlatinib (PF-06463922) treatment in a patient with ALK-rearranged non-small cell lung carcinoma (PMID: 28285684). 28285684
RB1 mut TP53 mut prostate carcinoma sensitive R547 Preclinical - Cell line xenograft Actionable In a preclinical study, R547 inhibited proliferation of prostate carcinoma cell lines harboring Tp53 and Rb1 mutations in culture and reduced tumor growth in xenograft models (PMID: 17121911). 17121911
RB1 mut TP53 mut breast carcinoma sensitive R547 Preclinical Actionable In a preclinical study, R547 inhibited proliferation of breast carcinoma cell lines harboring TP53 and RB1 mutations in culture (PMID: 17121911). 17121911
RB1 mut TP53 mut cervical cancer sensitive R547 Preclinical Actionable In a preclinical study, R547 inhibited proliferation of cervical carcinoma cell lines harboring Tp53 and Rb1 mutations (PMID: 17121911). 17121911
RB1 mutant osteosarcoma sensitive VCN-01 Preclinical - Cell line xenograft Actionable In a preclinical study, VCN-01 decreased viability of a human RB1-mutant primary osteosarcoma cell line in culture, and inhibited tumor growth and decreased lung metastases in xenograft models (PMID: 26603261). 26603261
RB1 mutant estrogen-receptor positive breast cancer predicted - resistant Palbociclib Phase III Actionable In a Phase III trial (PALOMA-3), acquired RB1 mutations were identified in patents with ER-positive, ERBB2 (HER2)-negative breast cancer at the end of treatment in the Faslodex (fulvestrant) plus Ibrance (palbociclib) but not the Faslodex (fulvestrant) plus placebo arm, suggesting a role in conferring resistance to Ibrance (palbociclib) (PMID: 30206110; NCT01942135). 30206110
RB1 dec exp Advanced Solid Tumor no benefit SHR6390 Preclinical - Cell culture Actionable In a preclinical study, SHR6390 (dalpiciclib) demonstrated limited cytotoxic activity against tumor cell lines with low Rb1 expression in culture (PMID: 30724426). 30724426
RB1 loss estrogen-receptor positive breast cancer resistant Palbociclib Preclinical - Cell culture Actionable In a preclinical study, RB1 loss was associated with acquired resistance to Ibrance (palbociclib) in an estrogen-receptor positive breast cancer cell line in culture (PMID: 27020857). 27020857
RB1 loss lung small cell carcinoma resistant Trilaciclib Preclinical - Cell line xenograft Actionable In a preclinical study, RB1-deficient small cell lung cancer cell lines were resistant to Trilaciclib (G1T28) in culture and in xenograft models (PMID: 26826116). 26826116
RB1 loss lung small cell carcinoma sensitive Topotecan + Trilaciclib Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Trilaciclib (G1T28) and Hycamtin (topotecan) inhibited tumor growth in RB1-deficient small cell lung cancer cell line xenograft models, with greater efficacy than Hycamtin (topotecan) alone (PMID: 26826116). 26826116
RB1 loss retinoblastoma sensitive Sirolimus Preclinical Actionable In a preclinical study, Sirolimus (rapamycin) decreased tumor occurrence, tumor hypoxia and tumor vascularization in a retinoblastoma mouse model with functionally inactivated Rb protein (PMID: 21468343, PMID: 1689463). 21468343 1689463
RB1 loss Merkel cell carcinoma sensitive LY3295668 Preclinical - Pdx & cell culture Actionable In a preclinical study, LY3295668 resulted in cell growth inhibition and increased cell cycle arrest and apoptosis in Merkel cell carcinoma patient-derived cell lines with loss of Rb1 expression in culture, and resulted in reduced tumor growth in a patient-derived xenograft (PDX) model (PMID: 34359608). 34359608
RB1 loss Advanced Solid Tumor no benefit Palbociclib Preclinical Actionable In preclinical studies, the CDK4/6 inhibitor, Ibrance (palbociclib), was not effective in a variety of solid tumors with Rb1-deficiency (PMID: 26649278). 26649278
RB1 loss retinoblastoma sensitive HDAC Inhibitor Entinostat Preclinical - Cell line xenograft Actionable In a preclinical study, Entinostat (MS-275) inhibited growth of retinoblastoma cell lines in culture and inhibited tumor growth in a retinoblastoma cell line xenograft model (PMID: 18483379), which have been demonstrated to be deficient in RB1 (PMID: 23498719). 23498719 18483379
RB1 loss retinoblastoma sensitive HDAC Inhibitor Trichostatin A Preclinical - Cell culture Actionable In a preclinical study, Trichostatin A (TSA) inhibited growth of retinoblastoma cell lines in culture (PMID: 18483379), which have been demonstrated to be deficient in RB1 (PMID: 23498719). 23498719 18483379
RB1 loss neuroendocrine tumor sensitive Sirolimus Preclinical Actionable In a preclinical study, Sirolimus (rapamycin) slowed pituitary tumors and decreased the occurrence of thyroid tumors in Rb1+/- mice (PMID: 23454836). 23454836
RB1 loss retinoblastoma sensitive HDAC Inhibitor Vorinostat Preclinical - Cell culture Actionable In a preclinical study, Zolinza (vorinostat) inhibited growth of retinoblastoma cell lines in culture (PMID: 18483379), which have been demonstrated to be deficient in RB1 (PMID: 23498719). 23498719 18483379
PTEN loss RB1 loss triple-receptor negative breast cancer no benefit Palbociclib + Pictilisib Preclinical Actionable In a preclinical study, the combination of Ibrance (palbociclib) and Pictilisib (GDC-0941) did not improve growth inhibition compared to single drug treatment in triple-receptor negative breast cancer cell lines harboring PTEN and RB1 loss in culture (PMID: 27020857). 27020857
PTEN loss RB1 loss triple-receptor negative breast cancer resistant Pictilisib Preclinical Actionable In a preclinical study, a triple-receptor negative breast cancer line harboring PTEN and RB1 loss was resistant to Pictilisib (GDC-0941) induced growth inhibition in culture (PMID: 27020857). 27020857
PTEN loss RB1 loss triple-receptor negative breast cancer resistant Palbociclib Preclinical Actionable In a preclinical study, a triple-receptor negative breast cancer line harboring PTEN and RB1 loss was resistant to Ibrance (palbociclib) induced growth inhibition in culture (PMID: 27020857). 27020857
BRAF mut RB1 loss melanoma decreased response Palbociclib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line with a BRAF mutation and loss of RB1 demonstrated minimal sensitivity when treated with the combination of Ibrance (palbociclib) and Mekinist (trametinib) in culture (PMID: 27488531). 27488531
BRAF mut RB1 loss melanoma decreased response Palbociclib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring a BRAF mutation and loss of RB1 demonstrated a decreased response to Ibrance (palbociclib) treatment in culture when compared to treatment of melanoma cell lines wild-type for BRAF (PMID: 27488531). 27488531
BRAF mut RB1 loss melanoma decreased response Trametinib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring a BRAF mutation and RB1 loss demonstrated reduced sensitivity when treated with Mekinist (trametinib) in culture (PMID: 27488531). 27488531
Clinical Trial Phase Therapies Title Recruitment Status Covered Countries Other Countries