palbociclib

Overview

Palbociclib is an oral CDK4/6 inhibitor that blocks G1-to-S-phase cell-cycle progression. It is FDA-approved for hormone-receptor-positive, HER2-negative breast cancer. In sarcoma, CDK4/6 pathway activation (notably CDK4 amplification in liposarcoma) has motivated its inclusion in functional drug screens.

Evidence in the corpus

  • Palbociclib was included in the UCLA PDTO sarcoma drug-screening panel (>400 compounds); CDK4 amplification — prevalent in liposarcoma (WDLS/DDCHS) — was cited as the genomic rationale for testing CDK4/6 inhibitors across sarcoma PDTOs (e.g., SARC0086_3 PEComa). Response rates were not reported at the subtype level in the published data. PMID:39305899
  • Pharmacologic CDK4/CDK6 inhibition with PD0332991 (palbociclib) induced G1 arrest in DDLS cell lines LPS141 and DDLS8817 following an shRNA screen of 385 genes on chromosome 12q that identified CDK4 as the top amplified dependency; CDK4 was the most overexpressed of 27 amplified anti-proliferative hits relative to normal fat. This constitutes one of the earliest functional genomic rationales for CDK4/6 inhibition in dedifferentiated liposarcoma PMID:20601955.
  • CDK4/6 inhibitor palbociclib under evaluation in RB1-intact HCC as a rationale-driven trial target; RB1 LOF occurs in 4% and homozygous deletion in 5% of HCCs PMID:24798001
  • CDKN2A loss (>36%), CDK4 amplification, and CCND1 amplification in pancreatic ductal adenocarcinoma (109 resected cases, WES) make PDA a high-prior candidate for CDK4/6 inhibition with palbociclib (PD-0332991); synergy with pathway-selective agents shown in PDA models PMID:25855536
  • RB1 loss-of-function mutations occur in 5% of HR+/HER2- metastatic breast cancer (mBC) and may confer primary resistance to palbociclib, since RB1 protein is required for CDK4/6 inhibitor bioactivity; authors recommend RB1 testing on metastatic samples before initiating CDK4/6 inhibitors PMID:28027327
  • p53/Rb-pathway-altered MIBC (CDKN2A loss with retained Rb) is being targeted with palbociclib (PD-0332991) in NCT02334527, motivated by the pervasive p53/cell-cycle pathway inactivation (89% of tumors) found in the TCGA MIBC cohort PMID:28988769

Resistance mechanisms

  • Not reported in corpus.

Cancer types (linked)

Sources

  • PMID:39305899 — Duminuco et al. 2024, UCLA PDTO sarcoma functional screen; CDK4/6 inhibitor testing context.
  • PMID:20601955 — Barretina et al. 2010, Nature Genetics; functional validation of CDK4 dependency in DDLS; G1 arrest by palbociclib (PD0332991).

This page was processed by crosslinker on 2026-05-14. - PMID:24798001

This page was processed by crosslinker on 2026-05-14. - PMID:25855536

This page was processed by crosslinker on 2026-05-14. - PMID:28027327 — Lefebvre et al. 2016, metastatic breast cancer WES; RB1 loss in 5% of HR+/HER2- mBC may confer primary palbociclib resistance.

*This page was processed by entity-page-writer on 2026-05-15. - PMID:28988769

This page was processed by wiki-cli on 2026-05-15.