Related Experiment Video

Updated: Jul 5, 2025

Development of a Human Preclinical Model of Osteoclastogenesis from Peripheral Blood Monocytes Co-cultured with Breast Cancer Cell Lines
06:00

Development of a Human Preclinical Model of Osteoclastogenesis from Peripheral Blood Monocytes Co-cultured with Breast Cancer Cell Lines

Published on: September 13, 2017

7.1K

Relationship between Medication-Related Osteonecrosis of the Jaw and CDK4/6 Inhibitors in Breast Cancer

Loreto Domínguez Senín1, David Morales Pancorbo2, María Yeray Rodríguez Garcés3

  • 1Hospital Pharmacy, Juan Ramón Jiménez University Hospital, 21005 Huelva, Spain.

Current Oncology (Toronto, Ont.)
|January 22, 2024
PubMed
Abstract

Insights

Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors may increase the risk of medication-related osteonecrosis of the jaw (MRONJ) in metastatic breast cancer patients on denosumab. Abemaciclib showed a significant association with higher MRONJ occurrence.

Area of Science:

  • Oncology
  • Pharmacology
  • Oral Surgery

Background:

  • Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse effect associated with antiresorptive agents like denosumab.
  • The concurrent use of CDK4/6 inhibitors with denosumab in metastatic breast cancer treatment is increasingly common.
  • Understanding potential synergistic risks between these drug classes is crucial for patient safety.

Purpose of the Study:

  • To evaluate cyclin-dependent kinase 4/6 (CDK4/6) inhibitors as a risk factor for medication-related osteonecrosis of the jaw (MRONJ).
  • To assess the incidence and timing of MRONJ in metastatic breast cancer patients treated with denosumab, with and without CDK4/6 inhibitors.

Main Methods:

  • A multicenter, retrospective, observational study.
  • Inclusion of all metastatic breast cancer patients treated with denosumab between January 2011 and December 2022.
  • Analysis of the relationship between CDK4/6 inhibitor use and MRONJ occurrence.

Main Results:

  • Of 243 patients, 95 (44.2%) used a CDK4/6 inhibitor, and 21 developed MRONJ.
  • MRONJ incidence was 13.7% with denosumab + CDK4/6 inhibitors vs. 6.6% with denosumab alone (p=0.085).
  • Patients using abemaciclib showed a significantly higher probability of MRONJ (p=0.0178).

Conclusions:

  • CDK4/6 inhibitors may increase MRONJ incidence and hasten its onset in denosumab-treated metastatic breast cancer patients.
  • Abemaciclib demonstrated a statistically significant association with increased MRONJ risk.
  • Larger prospective studies are warranted to clarify the risk of this drug combination.
Keywords:
CDK4/6 inhibitorsMRONJmetastatic breast canceroral epidemiology

More Related Videos

Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment11:13

Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment

Published on: June 9, 2023

1.6K
Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen19:44

Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen

Published on: May 30, 2012

18.7K

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
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.8K
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.
5.5K
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...
4.9K
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...
7.6K