Targeting CDK2 to circumvent treatment resistance in HR+ breast cancer

Leire Arrizabalaga; Esmeralda García-Torralba; Lorenzo Galluzzi; Aitziber Buqué

doi:10.1016/j.molmed.2024.12.009

Targeting CDK2 to circumvent treatment resistance in HR⁺ breast cancer

Trends Mol Med. 2024 Dec 27:S1471-4914(24)00342-3. doi: 10.1016/j.molmed.2024.12.009. Online ahead of print.

Authors

Leire Arrizabalaga¹, Esmeralda García-Torralba², Lorenzo Galluzzi³, Aitziber Buqué⁴

Affiliations

¹ Cancer Signaling and Microenvironment Program, Fox Chase Cancer Center, Philadelphia, PA, USA; Program of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, Spain; Navarra Institute for Health Research (IDISNA), Pamplona, Spain.
² Cancer Signaling and Microenvironment Program, Fox Chase Cancer Center, Philadelphia, PA, USA; Department of Medical Oncology, Hospital Universitario Morales Meseguer, Murcia, Spain; Department of Medicine, Medical School, University of Murcia, Murcia, Spain; IMIB-Arrixaca, Murcia, Spain.
³ Cancer Signaling and Microenvironment Program, Fox Chase Cancer Center, Philadelphia, PA, USA. Electronic address: [email protected].
⁴ Cancer Signaling and Microenvironment Program, Fox Chase Cancer Center, Philadelphia, PA, USA. Electronic address: [email protected].

PMID: 39732571
DOI: 10.1016/j.molmed.2024.12.009

Abstract

Genetic and epigenetic defects of the p53 system have previously been associated with resistance to CDK4/6 inhibitors in women with HR⁺ breast cancer. Recent data from Kudo et al. demonstrate that CDK2-targeting agents may offer an effective strategy to circumvent such resistance by enforcing cellular senescence downstream of RBL2 dephosphorylation.

Keywords: DREAM complex; MDM2; RB1; immune checkpoint inhibitors; non-oncogene addiction; type I interferon.