CDK4/6 inhibitors: A potential therapeutic approach for triple negative breast cancer. Issue 4 (17th November 2021)

• Record Type: Journal Article
• Authors: Saleh, Lubaid; Wilson, Caroline; Holen, Ingunn
• Is Part Of: MedComm. Volume 2:Issue 4(2022)
• Page Start: 514
• Page End: 530
• Publication Date: 2021-11-17
• Subjects: CDK/4/6 inhibitors -- metastatic -- triple negative breast cancer; 610
• DOI: 10.1002/mco2.97
• Languages: English
• ISSNs: 2688-2663

Abstract

Abstract: Triple negative breast cancer (TNBC) cells lack expression of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor‐2 (HER‐2). Thus, TNBC does not respond to hormone‐based therapy. TNBC is also an aggressive subtype associated with poorer prognoses compared to other breast cancers. Conventional chemotherapeutics are used to manage TNBC although systemic relapse is common with limited benefits being reported as well as adverse events being documented. Here, we discuss current therapies for TNBC in the neo‐ and adjuvant settings, as well as recent advancements in the targeting of PD‐L1‐positive tumors and inclusion of PARP inhibitors for TNBC patients with BRCA mutations. The recent development of cyclin‐dependent kinase (CDK) 4/6 inhibitors in ER‐positive breast cancers has demonstrated significant improvements in progression free survival in patients. Here, we review preclinical data of CDK 4/6 inhibitors and describe current clinical trials assessing these in TNBC disease. Abstract : Triple negative breast cancer (TNBC) is an aggressive subtype associated with poorer prognoses compared to other breast cancers. Conventional chemotherapeutics are used to manage TNBC although systemic relapse is common with limited benefits being reported. The identification of alternative pathways important for the survival of cancer cells has led to the development of CDK4/6 inhibitors that have shown great promise in preliminary clinical trials in TNBC patients, in the presence of chemotherapy and alone as monotherapy. With early preclinical studies further novel agents have been identified that may lead to new strategies in treating TNBC and providing improved prognoses for patients.