Related Experiment Video

Updated: Sep 2, 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

11.4K

Targeting CDK4 and 6 in Cancer Therapy: Emerging Preclinical Insights Related to Abemaciclib

Seth A Wander1, Neil O'Brien2, Lacey M Litchfield3

  • 1Department of Medical Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.

The Oncologist
|August 2, 2022
PubMed

Insights

Cyclin-dependent kinase 4 and 6 inhibitors (CDK4 and 6i) show promise in treating hormone receptor-positive breast cancer (HR+ BC). This review highlights abemaciclib

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Cyclin-dependent kinase 4 and 6 inhibitors (CDK4 and 6i) are approved for specific hormone receptor-positive (HR+) breast cancer (BC) subsets.
  • Combining CDK4 and 6i with endocrine therapy improves outcomes in metastatic HR+ BC.
  • CDK4 and 6i function by inhibiting retinoblastoma protein phosphorylation, blocking E2F target gene transcription and cell proliferation.

Purpose of the Study:

  • To review preclinical data on CDK4 and 6i in breast cancer.
  • To focus on the unique properties of abemaciclib.
  • To explore novel mechanisms and potential applications of abemaciclib.

Main Methods:

  • Summary of preclinical studies involving CDK4 and 6 inhibitors in breast cancer models.
  • Analysis of abemaciclib's chemical, pharmacologic, and mechanistic characteristics.
  • Review of emerging research on abemaciclib's antitumor activity and blood-brain barrier penetration.

Main Results:

  • Preclinical data support the use of CDK4 and 6i in breast cancer treatment.
  • Abemaciclib exhibits unique properties, including antitumor activity across various tumor types and blood-brain barrier penetration.
  • Abemaciclib has demonstrated efficacy as a monotherapy in preclinical breast cancer models.

Conclusions:

  • Understanding the mechanisms of CDK4 and 6 blockade reveals abemaciclib's distinct in-class properties.
  • Further research into abemaciclib's mechanisms could identify new therapeutic strategies.
  • Abemaciclib shows potential for enhanced efficacy and broader applications in cancer treatment.
Keywords:
CDK4 and 6abemaciclibantitumorbreast neoplasmspreclinical

More Related Videos

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

11.1K
Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies09:29

Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies

Published on: September 30, 2016

13.9K

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...
4.9K
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...
5.7K
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...
7.8K
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...
5.1K
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
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.
5.6K