During G1 phase, cyclin D (CycD)-CDK4/6 kinases together with cyclin E (CycE)-CDK2 phosphorylate the retinoblastoma protein, RB1. This activates the E2F transcriptional program, and allows entry of cells into S-phase.

Feb 29, 2024 · Here, we demonstrate that MYC amplification confers resistance to CDK4/6i in bladder, prostate and breast cancer cells. Mechanistically, MYC binds to the promoter of the E3 ubiquitin ligase...

Mar 1, 2018 · Results: We identified detectable acquired RB1 mutations in circulating tumor DNA (ctDNA) after exposure to CDK4/6 inhibitor (palbociclib, palbociclib, ribociclib) for 5, 8, and 13 months, respectively, in three patients.

Canonically, RB1 regulates cell cycle progression and represents the down-stream target for CDK4/6 inhibitors that are in clinical use. However, newly discovered features of the RB1-pathway suggest new therapeutic strategies to counter resistance and improve precision medicine.

The Ser/Thr-kinase component of cyclin D-CDK4 (DC) forms complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G1/S transition.

Sep 7, 2022 · CDK4/6 inhibitors combined with endocrine therapy have demonstrated higher antitumor activity than endocrine therapy alone for the treatment of advanced estrogen receptor-positive breast...

Jun 2, 2022 · Here, we sought to define the effects of pre-treatment RB1 allelic copy number status on outcomes of CDK4/6i-ET and the likelihood of developing RB1 loss-of-function (LOF) mutations on CDK4/6i through the analysis of an expanded …

SCLC is characterized by bi-allelic inactivation of two major tumor suppressor genes, TP53 and RB1, and lack of any actionable driver mutations. One third of patients can exhibit high tumor mutation burden. Recent investigations have mainly focused on characterization of biological underpinnings of SCLC.

Three different oral CDK4/6 inhibitors, palbociclib, ribociclib, and abemaciclib, have significantly improved progression-free survival by a number of months when combined with endocrine therapy. More recently, improvement in overall survival has …

We identified detectable acquired RB1 mutations in circulating tumor DNA (ctDNA) after exposure to CDK4/6 inhibitor (palbociclib, palbociclib, ribociclib) for 5, 8, and 13 months, respectively, in three patients.