Related Experiment Video

Updated: Feb 28, 2026

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

11.9K

Targeting PCK1 to overcome CDK4/6 inhibitor resistance for breast cancer therapy

Chen-Shiou Wu1, Hsiao-Fan Chen2, Kieu-Thanh Huynh3

  • 1Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan; Cancer Biology and Precision Therapeutics Center and Research Center for Cancer Biology, China Medical University, Taichung, Taiwan; Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.

Cancer Letters
|February 26, 2026
PubMed

Insights

Phosphoenolpyruvate carboxykinase 1 (PCK1) promotes breast cancer growth and resistance to CDK4/6 inhibitors. Targeting PCK1 with everolimus or auranofin synergizes with CDK4/6 inhibitors, offering new breast cancer treatment strategies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Phosphoenolpyruvate carboxykinase 1 (PCK1) has a dual role in cancer, acting as an oncogene in some cancers and a tumor suppressor in others.
  • Understanding PCK1's specific role in different cancer types is crucial for developing effective targeted therapies.

Purpose of the Study:

  • To investigate the role of PCK1 in breast cancer malignancy.
  • To elucidate the mechanism by which PCK1 contributes to oncogenesis and therapeutic resistance.
  • To identify potential therapeutic strategies targeting PCK1 in breast cancer.

Main Methods:

  • Utilized a breast cancer model to study PCK1's function.
  • Investigated PCK1's interaction with Cyclin D3 and CDK4/6.
  • Conducted drug screening to identify PCK1 inhibitors.
  • Evaluated the synergistic effects of PCK1 inhibitors and CDK4/6 inhibitors in breast cancer models.

Main Results:

  • PCK1 promotes cell proliferation, colony formation, and DNA synthesis in breast cancer.
  • PCK1 interacts with Cyclin D3, correlating positively in clinical samples.
  • PCK1 is identified as a key factor in CDK4/6 inhibitor resistance.
  • Everolimus and auranofin were identified as PCK1 inhibitors, showing synergistic effects with CDK4/6 inhibitors in suppressing breast cancer.
  • PCK1-Cyclin D3 interaction observed in pancreatic cancer but not liver cancer, potentially explaining PCK1's varied roles.

Conclusions:

  • PCK1 plays an oncogenic role in breast cancer and contributes to CDK4/6 inhibitor resistance.
  • Combined therapy with PCK1 inhibitors (everolimus, auranofin) and CDK4/6 inhibitors shows promise for breast cancer treatment.
  • The findings help resolve the context-dependent role of PCK1 in different cancer types.
Keywords:
Breast cancerCDK4/6 inhibitorCyclin D3PCK1drug resistance

More Related Videos

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence10:09

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence

Published on: January 7, 2019

8.8K
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

8.0K

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...
6.1K
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...
9.0K
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...
6.7K
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...
6.2K
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...
3.8K
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...
8.2K