Related Experiment Video

Updated: Mar 28, 2026

Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down
08:59

Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down

Published on: December 11, 2017

7.7K

Overcoming Endocrine Resistance in Hormone-Receptor Positive Advanced Breast Cancer-The Emerging Role of CDK4/6

Ciara C O'Sullivan1

  • 1Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, USA.

International Journal of Cancer and Clinical Research
|January 5, 2016
PubMed

Insights

Targeting the cyclin D-cyclin-dependent kinases 4/6 (CDK4/6) pathway with CDK4/6 inhibitors shows promise for hormone-receptor-positive breast cancer, offering efficacy with manageable side effects like neutropenia.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Dysregulation of the cyclin D-CDK pathway promotes cancer cell proliferation by inhibiting senescence.
  • The cyclin D-CDK4/6-Rb pathway is crucial for cell cycle control and frequently altered in breast cancer.
  • This pathway represents a rational therapeutic target for breast cancer treatment.

Purpose of the Study:

  • To review the preclinical and clinical development of selective cyclin-dependent kinase 4/6 inhibitors (CDK4/6i).
  • To examine preclinical evidence on combining CDK4/6i with chemotherapy and targeted therapies.
  • To discuss ongoing and future clinical trials evaluating CDK4/6i.

Main Methods:

  • Review of preclinical data and clinical trial results (Phase I, II, III) for CDK4/6 inhibitors.
  • Analysis of efficacy and safety profiles, including side effects like neutropenia.
  • Exploration of combination strategies with other anticancer agents.

Main Results:

  • Three selective oral CDK4/6 inhibitors (palbociclib, ribociclib, abemaciclib) are in clinical development.
  • Clinical trials in hormone-receptor-positive breast cancer demonstrate encouraging efficacy and a tolerable side-effect profile.
  • Neutropenia is the primary observed side effect.

Conclusions:

  • CDK4/6 inhibitors are promising agents for hormone-receptor-positive breast cancer.
  • These inhibitors have the potential to significantly alter the therapeutic landscape for this cancer type.
  • Further research and clinical trials are exploring expanded applications and combination therapies.
Keywords:
AbemaciclibBreast cancerCDK4/6 inhibitorsEndocrine resistancePalbociclibRibociclib

More Related Videos

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

7.3K
Using Mouse Mammary Tumor Cells to Teach Core Biology Concepts: A Simple Lab Module10:39

Using Mouse Mammary Tumor Cells to Teach Core Biology Concepts: A Simple Lab Module

Published on: June 18, 2015

13.9K

Related Concept Videos

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...
9.1K
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...
3.9K
Treatment Resistent Cancers02:56

Treatment Resistent Cancers

1.5K
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...
8.4K
Target Cell Response to Hormones01:22

Target Cell Response to Hormones

Hormones intricately bind to receptors on the surface or within target cells, initiating a cascade of cellular responses.
Notably, the cellular response can be regulated by altering the number of receptors expressed in the cell. For example, prolonged exposure to elevated hormone levels results in a gradual decline or down-regulation in the number of receptors for that specific hormone on the cell surface. Conversely, in response to low hormone levels, cells may use up-regulation, producing an...
6.2K
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...
6.3K