CDK4/6 inhibitors in breast cancer.

Published

Journal Article (Review)

Deregulation of the cyclin-dependent kinase (CDK) 4/6-retinoblastoma (RB) axis can occur through a number of mechanisms and contributes towards the unrestrained growth witnessed in a variety of cancers including breast cancers. Recent years have seen the development of selective CDK4/6 inhibitors, which have delivered promising preclinical and clinical results in breast cancer and other tumours. A number of trials assessing antitumour efficacy in various disease settings and combinations are ongoing. The cyclin D1-CDK-Rb axis and its role in the cell cycle of normal and cancer cells are delineated. The early pan-CDK inhibitor flavopiridol and subsequent preclinical and clinical development of selective CDK4/6 inhibitors are described. Ongoing studies in breast cancer with novel CDK4/6 inhibitors (palbociclib, abemaciclib and ribociclib) are explored. A literature search of these topics was performed through PubMed. Abstracts from major oncology meetings were also reviewed. Selective CDK4/6 inhibitors, as represented by the competing compounds currently in clinical development, comprise a novel, safe and, thus far, promisingly efficacious group of drugs. Considerable resources are being devoted towards exploring the efficacy of these drugs in combination with endocrine therapies, an approach that has yielded encouraging results and accelerated approval by the US Food and Drugs Administration for one of these agents (palbociclib). The results of confirmatory phase 3 trials are, however, awaited. We discuss further therapy combinations in development and highlight potential areas for caution including the potential for antagonistic interactions with cytotoxic chemotherapies.

Full Text

Duke Authors

Cited Authors

  • Dukelow, T; Kishan, D; Khasraw, M; Murphy, CG

Published Date

  • September 2015

Published In

Volume / Issue

  • 26 / 8

Start / End Page

  • 797 - 806

PubMed ID

  • 26053278

Pubmed Central ID

  • 26053278

Electronic International Standard Serial Number (EISSN)

  • 1473-5741

Digital Object Identifier (DOI)

  • 10.1097/CAD.0000000000000249

Language

  • eng

Conference Location

  • England