Related Experiment Video

Updated: Aug 3, 2025

Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
09:38

Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure

Published on: August 11, 2017

8.9K

CDK4/6 inhibitor resistance in estrogen receptor positive breast cancer, a 2023 perspective

Fiona H Zhou1,2, Teesha Downton1,2, Allegra Freelander1,2

  • 1Garvan Institute of Medical Research, Sydney, NSW, Australia.

Frontiers in Cell and Developmental Biology
|April 10, 2023
PubMed

Insights

Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are standard for ER+ breast cancer but resistance develops. Understanding resistance mechanisms is crucial for effective next-line treatments.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors plus endocrine therapy are first-line treatments for estrogen receptor-positive (ER+)/HER2-negative advanced breast cancer.
  • While effective, acquired resistance to CDK4/6 inhibitors is inevitable, necessitating new therapeutic strategies.

Purpose of the Study:

  • To review mechanisms of intrinsic and acquired resistance to CDK4/6 inhibitors and endocrine therapy in ER+ breast cancer.
  • To highlight potential therapeutic strategies to overcome CDK4/6 inhibitor resistance.

Main Methods:

  • Review of preclinical studies.
  • Analysis of clinical cohorts.
  • Synthesis of current research on resistance mechanisms and therapeutic strategies.

Main Results:

  • Diverse mechanisms contribute to both intrinsic and acquired resistance to CDK4/6 inhibitors.
  • Understanding these mechanisms is key to developing effective subsequent treatments.
  • Several potential therapeutic strategies are emerging to address resistance.

Conclusions:

  • Addressing CDK4/6 inhibitor resistance is a critical unmet need in ER+ advanced breast cancer treatment.
  • Further research into resistance mechanisms will guide the development of novel therapeutic approaches.
  • Personalized treatment strategies based on resistance profiles may improve patient outcomes.
Keywords:
CDK4/6 inhibitorbreast cancerendocrine therapyestrogen receptorresistance

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

7.3K
Orthotopic Transplantation of Breast Tumors as Preclinical Models for Breast Cancer07:45

Orthotopic Transplantation of Breast Tumors as Preclinical Models for Breast Cancer

Published on: May 18, 2020

6.1K

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...
4.8K
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...
5.6K
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...
3.4K
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.6K
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...
7.7K
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
7.6K