Related Experiment Video

Updated: Dec 18, 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

11.7K

Chemotherapy and CDK4/6 Inhibitors: Unexpected Bedfellows

Patrick J Roberts1, Vishnu Kumarasamy2, Agnieszka K Witkiewicz2,3

  • 1G1 Therapeutics, Research Triangle Park, North Carolina.

Molecular Cancer Therapeutics
|June 18, 2020
PubMed

Insights

Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) show promise when combined with chemotherapy. Preclinical and clinical studies suggest this combination enhances antitumor effects and reduces toxicity, representing a rational approach to cancer therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Cyclin-dependent kinases 4 and 6 (CDK4/6) are key therapeutic targets in cancer treatment.
  • CDK4/6 inhibitors (CDK4/6i) block cell-cycle progression and influence the tumor microenvironment.
  • Initial hypotheses suggested CDK4/6i might counteract chemotherapy, but evidence points to synergistic effects.

Purpose of the Study:

  • To explore the potential synergy between CDK4/6 inhibitors and chemotherapy.
  • To investigate the mechanisms underlying the combination of CDK4/6 inhibition and chemotherapy.
  • To evaluate the clinical relevance of combining CDK4/6i with chemotherapy for enhanced efficacy and reduced toxicity.

Main Methods:

  • Review of preclinical studies investigating CDK4/6i and chemotherapy interactions.
  • Analysis of ongoing clinical trials combining CDK4/6i with chemotherapy.
  • Exploration of noncanonical effects of CDK4/6i in combination therapy.

Main Results:

  • Multiple preclinical studies demonstrate significant cooperation between CDK4/6i and chemotherapy.
  • Clinical trials are actively testing this combination to improve antitumor efficacy and manage toxicity.
  • Noncanonical actions of CDK4/6i offer further avenues for combination strategies.

Conclusions:

  • The combination of CDK4/6 inhibition and chemotherapy represents a rational therapeutic strategy.
  • Synergistic effects observed in preclinical and clinical settings support this combination.
  • Further research into noncanonical effects may optimize combination therapies.

More Related Videos

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts10:27

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts

Published on: July 25, 2020

7.7K
Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics06:00

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics

Published on: May 14, 2016

11.4K

Related Concept Videos

Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
5.4K
Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
5.8K
M-Cdk Drives Transition Into Mitosis02:15

M-Cdk Drives Transition Into Mitosis

Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
6.1K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
8.5K
Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists01:28

Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists

Neurokinin 1 (NK1) receptors are distributed across the GI tract, vagal afferents, and key CNS regions including the central vomiting center and chemoreceptor trigger zone (CTZ) Chemotherapy agents stimulate enterochromaffin cells in the gastrointestinal (GI) tract to release large amounts of substance P (SP). SP is a neuropeptide released by specific sensory nerves in response to many different stressors, including those in the GI mucosa affected by chemotherapy.  SP binds and activates...
443
Cancer Therapies02:49

Cancer Therapies

Cancer therapies are various modes of treatment, such as surgery, radiation therapy, and chemotherapy that are administered to cancer patients.
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
9.7K