Cancer Management and Research (Jul 2021)
Potential Prospect of CDK4/6 Inhibitors in Triple-Negative Breast Cancer
Abstract
Ye Hu, Jiyue Gao, Meiling Wang, Man Li Department of Oncology & Department of Breast Surgery, The Second Hospital of Dalian Medical University, Dalian, People’s Republic of ChinaCorrespondence: Man LiDepartment of Oncology & Department of Breast Surgery, The Second Hospital of Dalian Medical University, Dalian, People’s Republic of ChinaTel +86-411-84671291Fax +86-411-84671230Email [email protected]: Triple-negative breast cancer (TNBC) is an aggressive, difficult-to-treat subtype of cancer with a poor prognosis; there is an urgent need for effective, targeted molecular therapies. The cyclin D/cyclin-dependent kinase (CDK)4/6–retinoblastoma protein (Rb) pathway plays a critical role in regulating cell cycle checkpoints, a process which is often disrupted in cancer cells. Selective CDK4/6 inhibitors can prevent retinoblastoma protein phosphorylation by invoking cell cycle arrest in the first growth phase (G1), and may therefore represent an effective treatment option. In this article, we review the molecular mechanisms and therapeutic efficacy of CDK4/6 inhibitors in combination with other targeted therapies for the treatment of triple-negative breast cancer. Three selective CDK4/6 inhibitors have so far received the approval of the Food and Drug Administration (FDA) for patients with estrogen receptor (ER)+/human epidermal growth factor receptor 2 (HER2) breast cancer. Trilaciclib, a small molecule short-acting inhibitor of CDK4/6, has also been approved recently for people with small cell lung cancer, and is also expected to be clinically effective against breast cancer. Although the efficacy of CDK4/6 inhibitors in patients with triple-negative breast cancer remains uncertain, their use in conjunction with other targeted therapies may improve outcomes and is therefore currently being explored. Identifying biomarkers for response or resistance to CDK4/6 inhibitor treatment may optimize the personalization of treatment strategies for this disease. Ongoing and future clinical trials and biomarker studies will shed further light on these topics, and help to realize the full potential of CDK4/6 inhibitor treatment in triple-negative breast cancer.Keywords: triple-negative breast cancer, palbociclib, biomarkers, combination therapy
