December 1, 2023

This twice-monthly newsletter highlights recently published research where Dana-Farber faculty are listed as first or senior authors. The information is pulled from PubMed and this issue notes papers published from November 1 through November 15.

If you are a Dana-Farber faculty member and you think your paper is missing from Research News, please let us know by emailing [email protected].

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Annals of Oncology

Is There a Role for Continuation of CDK4/6 Inhibition After Progression on a Prior CDK4/6 Inhibitor in HR+/HER2- Metastatic Breast Cancer?

Giordano A, Lin NU, Tolaney SM, Mayer EL

Cyclin-dependent kinase 4 (CDK4) and CDK6 interact with cyclin D1 to hyperphosphorylate the retinoblastoma (RB1) gene product pRb early in the G1 phase of the cell cycle. This results in pRb inactivation and release of transcription factors that allow progression to the S phase. Cyclin D1 and CDK4 play particularly important roles in mammary gland biology and breast cancer and numerous molecular features suggest that the cyclin D-CDK4/6 pathway can be hyperactivated in human hormone receptor (HR)-positive breast cancers. The CDK4/6 inhibitors (CDK4/6i) palbociclib (Pfizer, Collegeville, PA), ribociclib (Novartis East, Hanover, NJ), and abemaciclib (Eli Lilly, Indianapolis, IN) are currently approved by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) in either the first-line or pre-treated setting in combination with endocrine therapy (ET, aromatase inhibitors or fulvestrant) for HR-positive, HER2-negative (HR+/HER2-) metastatic breast cancer (mBC). They all are ATP competitive kinase inhibitors that bind to the hinge region of CDK4/6 and inhibit phosphorylation of downstream substrates. Recently, abemaciclib received EMA and FDA approval for node-positive, high-risk, early-stage breast cancer in combination with adjuvant aromatase inhibitor, and positive data for ribociclib in the adjuvant setting have been reported.

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