Related Experiment Video

Updated: Dec 24, 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

Mechanisms of Sensitivity and Resistance to CDK4/6 Inhibition

Mónica Álvarez-Fernández1, Marcos Malumbres1

  • 1Cell Division and Cancer Group, Spanish National Cancer Research Centre (CNIO), Melchor Fernández Almagro 3, 28029 Madrid, Spain.

Cancer Cell
|April 15, 2020
PubMed

Insights

CDK4/6 inhibitors show promise for breast cancer but face resistance. Combining these inhibitors with other therapies may overcome resistance and expand their use to other cancer types.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • CDK4/6 inhibitors are effective in advanced hormone-positive breast cancer.
  • Resistance mechanisms limit the efficacy of CDK4/6 inhibitors.
  • Application of CDK4/6 inhibitors to other cancer types is uncertain.

Purpose of the Study:

  • To analyze CDK4/6 inhibitor sensitivity and resistance mechanisms.
  • To explore combination strategies for CDK4/6 inhibitors.
  • To improve the therapeutic use of CDK4/6 inhibition in various cancers.

Main Methods:

  • Integrative analysis of sensitivity and resistance mechanisms.
  • Review of existing targeted therapies, immunotherapy, and chemotherapy.
  • Discussion of potential combination treatments.

Main Results:

  • CDK4/6 inhibition is a validated strategy in specific cancers.
  • Understanding resistance is key to optimizing therapy.
  • Combination therapies show potential to enhance efficacy and broaden application.

Conclusions:

  • CDK4/6 inhibitors have significant therapeutic potential.
  • Overcoming resistance through combination strategies is crucial.
  • Further research is needed to establish CDK4/6 inhibition in diverse cancer types.
Keywords:
breast cancercell-cycle kinasescyclin-dependent kinasesresistance to cancer therapies

More Related Videos

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay12:26

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay

Published on: May 3, 2018

19.2K
Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis11:44

Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis

Published on: March 30, 2019

7.9K

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...
5.5K
Positive Regulator Molecules02:39

Positive Regulator Molecules

Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
6.4K
Positive Regulator Molecules01:45

Positive Regulator Molecules

To consistently produce healthy cells, the cell cycle—the process that generates daughter cells—must be precisely regulated.
133.1K
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...
6.2K
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.6K
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
38.1K