Cyclin-dependent kinase 4/6 inhibitors: what have we learnt across studies, therapy situations and substances

Malgorzata Banys-Paluchowski1, Natalia Krawczyk2, Peter Paluchowski3

  • 1Department of Gynecology and Obstetrics, Asklepios Klinik Barmbek, Hamburg.

Abstract

Insights

New CDK 4/6 inhibitors, including palbociclib, ribociclib, and abemaciclib, offer effective treatment for metastatic breast cancer. While improving progression-free survival, careful consideration of individual patient profiles is essential due to differing toxicity.

Area of Science:

  • Oncology
  • Pharmacology
  • Cell Biology

Background:

  • Cyclin-dependent kinases (CDKs) regulate cell division.
  • CDK 4/6 inhibitors have emerged as a significant therapeutic advance.
  • Approved CDK 4/6 inhibitors include palbociclib, ribociclib, and abemaciclib.

Purpose of the Study:

  • To provide a clinical overview of CDK 4/6 inhibitors in breast cancer.
  • To highlight current data on antitumor efficacy and toxicities.
  • To discuss the role of these agents in metastatic hormone receptor-positive HER2-negative breast cancer.

Main Methods:

  • Review of clinical trial data for CDK 4/6 inhibitors.
  • Analysis of progression-free survival data.
  • Evaluation of adverse event profiles.

Main Results:

  • CDK 4/6 inhibitors significantly prolonged progression-free survival in combination with endocrine therapy.
  • Common adverse events include neutropenia, fatigue, and gastrointestinal issues.
  • Clinical efficacy appears similar across agents, but toxicity profiles vary.

Conclusions:

  • CDK 4/6 inhibitors are a valuable treatment for metastatic HR+/HER2- breast cancer.
  • Individual patient characteristics and preferences should guide treatment selection.
  • Understanding differing toxicity profiles is crucial for optimal patient management.

Related Concept Videos

Dipeptidyl Peptidase 4 Inhibitors01:23

Dipeptidyl Peptidase 4 Inhibitors

Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a...
670
cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
8.5K
Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
15.1K
Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers01:26

Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers

Receptor tyrosine kinase inhibitors (TKIs) and calcium channel blockers (CCBs) are two critical categories of drugs employed in the treatment of pulmonary artery hypertension (PAH). PAH is a disease that causes high blood pressure in the pulmonary arteries, resulting in chest pain, fatigue, and shortness of breath.
TKIs, such as imatinib (Gleevec), are particularly effective in tackling the growth and mitogenic factors that become upregulated in PAH patients. These factors contribute to the...
535
Eukaryotic Transcription Inhibitors01:52

Eukaryotic Transcription Inhibitors

Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
11.0K
Deleterious Substances in Aggregate01:25

Deleterious Substances in Aggregate

Deleterious substances in aggregates can be detrimental to the quality and durability of concrete. These substances include organic impurities like loam, which interfere with cement hydration and are usually present in the sand. These prevent a good bond between aggregate and cement paste. Organic impurities can be detected using the colorimetric test, where the darkness of a solution after agitation indicates the level of organic content.
Another type of impurity is clay and fine material that...
553