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Profile Name RB1 positive
Gene Variant Detail

RB1 positive (unknown)

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
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 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 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 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 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 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 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 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 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 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 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 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 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
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 retinoblastoma sensitive 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 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 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 retinoblastoma sensitive 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 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
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
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
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
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
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 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 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 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 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 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 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 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 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 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
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 Fostamatinib Preclinical Actionable In a preclinical study, retinoblastoma cell lines demonstrated sensitivity to Fostamatinib resulting in cell death (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 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 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 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 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 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
Clinical Trial Phase Therapies Title Recruitment Status Covered Countries Other Countries
NCT02933736 Phase 0 Ribociclib Ribociclib (LEE011) in Preoperative Glioma and Meningioma Patients Recruiting USA 0
NCT02334527 Phase II Palbociclib Phase II Trial of Palbociclib (PD-0332991) in Patients With Metastatic Urothelial Cancer (UC) After Failure of First-Line Chemotherapy Terminated USA 0
NCT03526250 Phase II Palbociclib Palbociclib in Treating Patients With Relapsed or Refractory Rb Positive Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Activating Alterations in Cell Cycle Genes (A Pediatric MATCH Treatment Trial) Active, not recruiting USA 1
NCT01356628 Phase II Palbociclib A Clinical Research Study to Determine Whether PD 0332991 May Be Effective in Treating Patients With Liver Cancer Active, not recruiting USA 0
NCT03535506 Phase II Palbociclib Preoperative Palbociclib in Patients With DCIS of the Breast That Are Candidates for Surgery (WI223281) Recruiting USA 0
NCT02255461 Phase I Palbociclib Palbociclib Isethionate in Treating Younger Patients With Recurrent, Progressive, or Refractory Central Nervous System Tumors Terminated USA 0
NCT03781960 Phase II Abemaciclib + Nivolumab Abemaciclib and Nivolumab for Subjects With Hepatocellular Carcinoma Completed USA 0
NCT03130439 Phase II Abemaciclib Abemaciclib for Patients With Retinoblastoma-Positive, Triple Negative Metastatic Breast Cancer Terminated USA 0
NCT03110744 Phase II Palbociclib CDK4/6 Inhibition in Locally Advanced/Metastatic Chordoma (NCT-PMO-1601) Recruiting DEU 0
NCT03009201 Phase I Doxorubicin + Ribociclib Ribociclib and Doxorubicin in Treating Patients With Metastatic or Advanced Soft Tissue Sarcomas That Cannot Be Removed by Surgery Active, not recruiting USA 0
NCT02030483 Phase I Palbociclib Dexamethasone Lenalidomide Palbociclib in Combination With Lenalidomide and Dexamethasone for Multiple Myeloma Terminated USA 0
NCT02524119 Phase II Ribociclib LEE001 and Chemoembolization In Patients With Advanced Hepatocellular Carcinoma (LEE001) Terminated USA 0
NCT02599363 Phase I Paclitaxel + Ribociclib A Trial of Ribocilcib (LEE011) and Weekly Paclitaxel in Patients With Rb+ Advanced Breast Cancer Completed USA 0
NCT02555189 Phase Ib/II Ribociclib Enzalutamide Enzalutamide With and Without Ribociclib for Metastatic, Castrate-Resistant, Chemotherapy-Naive Prostate Cancer That Retains RB Expression Recruiting USA 0
NCT04040205 Phase II Abemaciclib Abemaciclib for Bone and Soft Tissue Sarcoma With Cyclin-Dependent Kinase (CDK) Pathway Alteration Recruiting USA 0
NCT01522989 Phase I Fluorouracil + Oxaliplatin + Palbociclib PD-0332991, 5-FU, and Oxaliplatin for Advanced Solid Tumor Malignancies Unknown status USA 0
NCT03355794 Phase I Everolimus + Ribociclib A Study of Ribociclib and Everolimus Following Radiation Therapy in Children With Newly Diagnosed Non-biopsied Diffuse Pontine Gliomas (DIPG) and RB+ Biopsied DIPG and High Grade Gliomas (HGG) Active, not recruiting USA 0
NCT03834740 Phase I Everolimus + Ribociclib A Phase 0 /II Study of Ribociclib (LEE011) in Combination With Everolimus in Preoperative Recurrent High-Grade Glioma Patients Scheduled for Resection Active, not recruiting USA 0
NCT04316169 Phase I Abemaciclib + Anastrozole + Hydroxychloroquine Abemaciclib + Fulvestrant + Hydroxychloroquine Abemaciclib + Hydroxychloroquine Abemaciclib + Hydroxychloroquine + Letrozole Hydroxychloroquine, Abemaciclib and Endocrine Therapy in Hormone Receptor Positive (HR+)/Her 2 Negative Breast Cancer Recruiting USA 0
NCT03114527 Phase II Everolimus + Ribociclib Phase II Trial of Ribociclib and Everolimus in Advanced Dedifferentiated Liposarcoma (DDL) and Leiomyosarcoma (LMS) Active, not recruiting USA 0
NCT04391595 Phase I Abemaciclib + LY3214996 LY3214996 Plus Abemaciclib in Recurrent Glioblastoma Patients Recruiting USA 0
NCT03155620 Phase II Tazemetostat Larotrectinib LY3023414 Vemurafenib Palbociclib Olaparib Ulixertinib Erdafitinib Selumetinib Ensartinib Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial) Recruiting USA 1