Related Experiment Video

Updated: Oct 1, 2025

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors
10:33

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

Published on: October 26, 2015

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The emerging CDK4/6 inhibitor for breast cancer treatment

M Saeed Sheikh1, Siem A Satti1,2

  • 1Department of Pharmacology, Sate University of New York, Upstate Medical University, Syracuse, New York.

Molecular and Cellular Pharmacology
|March 7, 2022
PubMed

Insights

Newer cyclin-dependent kinase (CDK) 4/6 inhibitor dalpiciclib, combined with fulvestrant, significantly improved progression-free survival in advanced breast cancer patients. This review covers its clinical use and side effects alongside established CDK4/6 inhibitors.

Area of Science:

  • Oncology
  • Pharmacology

Background:

  • Cyclin-dependent kinase (CDK) inhibitors are crucial cancer therapeutics.
  • Three CDK4/6 inhibitors (palbociclib, ribociclib, abemaciclib) are FDA-approved for hormone receptor-positive, HER2-negative advanced breast cancer, used with endocrine therapy.
  • Resistance to endocrine therapy necessitates novel treatment strategies.

Purpose of the Study:

  • To review the clinical use and side effects of approved CDK4/6 inhibitors: palbociclib, ribociclib, and abemaciclib.
  • To present interim findings on the efficacy of a novel CDK4/6 inhibitor, dalpiciclib, in combination with fulvestrant.
  • To evaluate dalpiciclib as a treatment for advanced breast cancer patients who have progressed on prior endocrine therapy.

Main Methods:

  • Review of clinical data and published literature on CDK4/6 inhibitors.
  • Analysis of interim results from the Phase III DAWNA-1 study (randomized, double-blind, placebo-controlled trial).
  • Investigation of dalpiciclib's efficacy and safety in combination with fulvestrant.

Main Results:

  • Dalpiciclib is an oral, ATP-competitive CDK4/6 inhibitor.
  • The DAWNA-1 study interim results show dalpiciclib plus fulvestrant significantly prolonged progression-free survival.
  • Established CDK4/6 inhibitors (palbociclib, ribociclib, abemaciclib) are effective in specific breast cancer subtypes.

Conclusions:

  • Dalpiciclib shows promise as a new therapeutic option for advanced breast cancer.
  • Combination therapy with CDK4/6 inhibitors and endocrine agents remains a key strategy.
  • Further research and long-term data are needed to fully establish dalpiciclib's role and safety profile.
Keywords:
AbemaciclibBreast cancerDalpiciclibFulvestrantPalbociclibRibociclib

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