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Gene | RB1 |
Variant | loss |
Impact List | unknown |
Protein Effect | loss of function |
Gene Variant Descriptions | RB1 loss indicates loss of the RB1 gene, mRNA, and protein. |
Associated Drug Resistance |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 |
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 |
Molecular Profile | Protein Effect | Treatment Approaches |
---|---|---|
RB1 loss | loss of function | HDAC Inhibitor |
PTEN loss RB1 loss | ||
BRAF mut RB1 loss |