Our LoF program targets cancers which are deficient in the tumor suppressor retinoblastoma 1 (RB1).
The RB1 tumor suppressor gene plays a critical role in coordinating multiple cellular pathways in cancer. Genomic loss or mutation of RB1 is a common alteration in several types of solid cancers and is associated with poor patient outcomes. There are no approved targeted therapies for RB1 LoF cancer patients.
About Retinoblastoma protein 1 (RB1)
RB1 protein regulates a variety of cellular functions, such as cell proliferation, DNA damage, cell cycle and apoptosis. Mutations that lead to inactivation of RB1 are common in cancers and frequent in aggressive and metastatic tumors.
RB1 LoF – snapshot
7% of all tumors display RB1 LoF and are enriched in cancers with a high unmet need.
Two key indications with high unmet need are small cell lung cancer (SCLC) and triple negative breast cancer (TNBC).
Prevalence of RB1 LoF in SCLC is between
80-100%
and in TNBC exceeds
40%
RB1 Companion Diagnostic (CDx)
Diagnosis of RB1 is well established and is part of the widely implemented NGS (Next Generation Sequencing) clinical test panels such as the FDA-approved FoundationOne CDx.
ALT Program
Therapeutic Strategy
Publications
Brough R et al. (2018) Identification of highly penetrant Rb-related synthetic lethal interactions in triple negative breast cancer.
Oncogene (2018) 37:5701–5718
View article
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