Molecular Profile Detail

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Profile Name RB1 loss
Gene Variant Detail

RB1 loss (loss of function)

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 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 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 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 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 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 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 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 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 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
Clinical Trial Phase Therapies Title Recruitment Status Covered Countries Other Countries
NCT02059213 Phase II Goserelin Palbociclib Bicalutamide Leuprolide A Phase II Study of Androgen Deprivation Therapy With or Without PD 0332991 in RB-Positive Metastatic Prostate Cancer Completed USA 0
NCT04388852 Phase I DS-3201b + Ipilimumab DS3201 and Ipilimumab for the Treatment of Metastatic Prostate, Urothelial and Renal Cell Cancers Recruiting USA 0
NCT04116541 Phase II Alectinib Cabozantinib HDM201 + Ribociclib A Study Evaluating the Activity of Anti-cancer Treatments Targeting Tumor Molecular Alterations/Characteristics in Advanced / Metastatic Tumors. (MegaMOST) Recruiting 1
NCT02873975 Phase II Prexasertib A Study of LY2606368 (Prexasertib) in Patients With Solid Tumors With Replicative Stress or Homologous Repair Deficiency Active, not recruiting USA 0
NCT04592237 Phase II Niraparib Cabazitaxel + Carboplatin + JNJ-63723283 JNJ-63723283 + Niraparib Cabazitaxel, Carboplatin, and Cetrelimab Followed by Niraparib With or Without Cetrelimab for the Treatment of Aggressive Variant Metastatic Prostate Cancer Recruiting USA 0
NCT03356223 Phase II Abemaciclib Evaluation of ABEMACICLIB Monotherapy in Patients With Locally Advanced/Metastatic Head and Neck Cancer After Failure of Platinum and Cetuximab or Anti-EGFR-based Therapy and Harboring an Homozygous Deletion of CDKN2A, and/or an Amplification of CCND1 and/or of CDK6 (ABORL) Recruiting 1
NCT04129151 Phase II Ganitumab + Palbociclib Palbociclib + Ganitumab In Ewing Sarcoma Active, not recruiting USA 0
NCT04469764 Phase II Abemaciclib + Anastrozole Abemaciclib + Letrozole Abemaciclib Abemaciclib for the Treatment of Recurrent Ovarian or Endometrial Cancer Recruiting USA 0
NCT03360721 Phase II Abiraterone + Apalutamide + Prednisone Study of Apalutamide and Abiraterone Acetate in Castration-Resistant Bone Metastatic Prostate Cancer Patients Suspended USA 0
NCT01976169 Phase I Ado-trastuzumab emtansine + Palbociclib Phase 1b Study of PD-0332991 in Combination With T-DM1(Trastuzumab-DM1) Active, not recruiting USA 0