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The emerging role of CDK4/6i in HER2-positive breast cancer.

ABSTRACT: Prior to the advent of the monoclonal antibody trastuzumab, human epidermal growth-factor receptor 2 (HER2)-positive (HER2+) breast cancer (BC) was associated with an aggressive clinical course and poor survival outcomes. In the era of effective HER2-directed therapies, median survival rates for patients with metastatic HER2+ BC now approach 5 years. Despite these improvements, the majority of affected patients unfortunately die from disease. Therapies to overcome treatment resistance are being actively pursued. One strategy has been to target the cyclin-dependent kinases 4/6 (CDK4/6), as they are downstream of HER2 and many of the cellular pathways driving resistance to HER2-targeted therapies, and play a key role in proliferation by controlling transition through the G1 restriction point to the S phase of the cell cycle. In this article, we review the published literature with regard to the rationale for CDK4/6-directed therapies in HER2+ BC and discuss ongoing clinical research and new challenges in the field.

SUBMITTER: O'Sullivan CC

PROVIDER: S-EPMC6887797 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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The emerging role of CDK4/6i in HER2-positive breast cancer.

O'Sullivan Ciara C CC Suman Vera J VJ Goetz Matthew P MP

Therapeutic advances in medical oncology 20191127

Prior to the advent of the monoclonal antibody trastuzumab, human epidermal growth-factor receptor 2 (HER2)-positive (HER2+) breast cancer (BC) was associated with an aggressive clinical course and poor survival outcomes. In the era of effective HER2-directed therapies, median survival rates for patients with metastatic HER2+ BC now approach 5 years. Despite these improvements, the majority of affected patients unfortunately die from disease. Therapies to overcome treatment resistance are being ...[more]

PMID: 31832106

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