Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Apr:196:104324.
doi: 10.1016/j.critrevonc.2024.104324. Epub 2024 Mar 8.

Cyclin-dependent kinase 2 (CDK2) inhibitors and others novel CDK inhibitors (CDKi) in breast cancer: clinical trials, current impact, and future directions

Riccardo Gerosa  1 , Rita De Sanctis  2 , Flavia Jacobs  1 , Chiara Benvenuti  1 , Mariangela Gaudio  1 , Giuseppe Saltalamacchia  3 , Rosalba Torrisi  3 , Giovanna Masci  3 , Chiara Miggiano  1 , Francesco Agustoni  4 , Paolo Pedrazzoli  4 , Armando Santoro  1 , Alberto Zambelli  1
Affiliations
Free article
Review

Cyclin-dependent kinase 2 (CDK2) inhibitors and others novel CDK inhibitors (CDKi) in breast cancer: clinical trials, current impact, and future directions

Riccardo Gerosa et al. Crit Rev Oncol Hematol. 2024 Apr.
Free article

Abstract

Aberrant cyclin-dependent kinase 2 (CDK2) activation has been identified as a main resistance mechanism to CDK4/6 inhibition in hormone-receptor positive (HR+) breast cancer. Additionally, consistent preclinical evidence states its crucial role in MYC and CCNE1 overexpressed cancer survival, such as triple-negative breast cancers (TNBC), thus representing an appealing and relatively unexplored target treatment opportunity. Despite emerging initial results of novel CDK2 inhibitors (CDK2i) activity, a comprehensive outcomes collection is currently absent from the scientific literature. We aim to provide an overview of ongoing clinical trials involving CDK2i in the context of metastatic breast cancer (mBC), either as monotherapy or in combination with other agents. The review extends beyond CDK2i to encompass novel emerging CDK4 inhibitors, combined CDK2/4/6 inhibitors, and the well-known pan-CDK inhibitors including those specifically directed at CDK2. Delving into the results, we critically appraise the observed clinical efficacy and offer valuable insights into their potential impact and future applications.

Keywords: Breast cancer (BC); Cyclin-dependent; Cyclin-dependent kinase 2 inhibitor (CDK2i); Cyclindependent; Kinase 2/4/6 inhibitor (CDK2/4/6i); Kinase 4 inhibitor (CDK4i); Metastatic breast cancer (mBC); Pan-Cyclin-dependent kinase inhibitor (Pan-CDKi).

PubMed Disclaimer

Conflict of interest statement

Declaration of Competing Interest Armando Santoro: Advisory Board: Bristol-Myers Squibb (BMS), Servier, Gilead, Pfizer, Eisai, Bayer, Merck Sharp & Dohme (MSD). Consultancy: Arqule, Sanofi, Incyte. Speaker’s Bureau: Takeda, BMS, Roche, Abb-Vie, Amgen, Celgene, Servier, Gilead, Astrazeneca, Pfizer, Arqule, Lilly, Sandoz, Eisai, Novartis, Bayer, MSD (all outside the submitted work); Alberto Zambelli has received personal fees and non-financial support from Novartis, AstraZeneca, Lilly, Pfizer, Daiichi Sankyo, MDS Merck Sharp&Dome, Roche, Seagen, Exact Sciences, Gilaed, Istituto Gentili; Rosalba Torrisi has received funding from Astra Zeneca, Pfizer, Eli Lilly, Exact Sciences and MSD; Rita De Sanctis honoraria for advisory board consultancy from Novartis, Istituto Clinico Gentili, Amgen, EISAI, Lilly and Gilead (all outside the present work). The other authors declare no competing interests.

MeSH terms