Retinoblastoma protein 1 (RB1) (RB1)

Retinoblastoma protein 1 (RB1) is a foundational tumor suppressor that acts as a master regulator of the cell cycle, specifically controlling the G1 to S phase transition [1.1.2, 1.2.1]. It functions by binding and inhibiting E2F transcription factors, thereby preventing the expression of genes required for DNA replication [1.2.1, 1.3.1]. In many cancers, RB1 is inactivated through genetic deletion, mutation, or hyperphosphorylation, leading to uncontrolled cell proliferation and genomic instability [1.1.1, 1.2.3]. While RB1 itself is not a direct target for inhibitory drugs due to its loss-of-function nature in tumors, its absence creates unique synthetic lethal vulnerabilities [1.1.2, 1.3.4]. Therapeutic strategies for RB1-deregulated tumor cells focus on targeting these vulnerabilities using inhibitors of Aurora kinases, ATR, and PKMYT1, which exploit the compromised cell cycle checkpoints and increased replication stress characteristic of RB1-deficient states [1.1.2, 1.4.1]. Additionally, RB1 loss is a major mechanism of resistance to CDK4/6 inhibitors, making its status a critical biomarker for patient stratification in breast and lung cancers [1.3.3, 1.4.1].

Other names

pRBRBRetinoblastoma 1OSRCp105-RbPP110

Synthetic lethality by exploiting vulnerabilities in DNA repair and mitotic checkpoints induced by the loss of RB1 function [1.1.2, 1.3.2].