Related Experiment Video

Updated: Sep 10, 2025

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

7.3K

ATR-CHK1 Axis Inhibitors in Gastric Cancer Treatment

Mateusz Kciuk1, Renata Gruszka1, Marta Aleksandrowicz2

  • 1Department of Molecular Biotechnology and Genetics, Faculty of Biology and Environmental Protection, University of Lodz, Banacha Street 12/16, 90-237 Lodz, Poland.

International Journal of Molecular Sciences
|August 28, 2025
PubMed

Insights

ATR-CHK1 inhibitors show promise for treating gastric cancer by targeting DNA damage response pathways. This approach offers new therapeutic strategies for patients with advanced disease, especially when combined with other treatments.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Gastric cancer presents a significant global health burden with poor prognosis for advanced cases.
  • Tumors exhibit vulnerabilities in DNA damage response (DDR) pathways, including frequent TP53 mutations, ARID1A loss, ATM deficiency, and replication stress.
  • These vulnerabilities create a dependency on the ATR-CHK1 axis for cancer cell survival.

Purpose of the Study:

  • To review current clinical and preclinical evidence for ATR and CHK1 inhibitors in gastric cancer treatment.
  • To explore the potential of these inhibitors based on synthetic lethality and immune modulation.
  • To discuss resistance mechanisms and strategies for overcoming therapeutic failure.

Main Methods:

  • Synthesis of existing clinical and preclinical data on ATR/CHK1 inhibitors.
  • Analysis of molecular vulnerabilities in gastric cancer, focusing on DDR pathways.
  • Review of combination strategies involving chemotherapy, radiotherapy, and immunotherapy.

Main Results:

  • ATR-CHK1 axis inhibition represents a promising therapeutic strategy for gastric cancer.
  • Combination regimens with chemotherapy, radiotherapy, or immune checkpoint inhibitors may enhance efficacy.
  • Biomarker-guided selection and adaptive dosing are crucial for optimizing treatment precision and reducing toxicity.

Conclusions:

  • ATR-CHK1 inhibitors offer a rational approach for treating specific gastric cancer subsets.
  • Understanding resistance mechanisms is key to developing effective therapeutic strategies.
  • Further research and clinical integration of these inhibitors are warranted for biomarker-defined patient populations.
Keywords:
ARID1A lossATR–CHK1 inhibitorsDNA damage responseTP53 mutationbiomarker-guided therapygastric cancerimmune modulationreplication stresssynthetic lethalitytreatment resistance

More Related Videos

Author Spotlight: Genetic Profiling for Fluorouracil Response in Gastric Cancer06:21

Author Spotlight: Genetic Profiling for Fluorouracil Response in Gastric Cancer

Published on: May 10, 2024

845
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

Related Concept Videos

Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists01:28

Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists

Neurokinin 1 (NK1) receptors are distributed across the GI tract, vagal afferents, and key CNS regions including the central vomiting center and chemoreceptor trigger zone (CTZ) Chemotherapy agents stimulate enterochromaffin cells in the gastrointestinal (GI) tract to release large amounts of substance P (SP). SP is a neuropeptide released by specific sensory nerves in response to many different stressors, including those in the GI mucosa affected by chemotherapy.  SP binds and activates...
259
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
Chemotherapy-Induced Nausea and Vomiting: 5-HT3 Receptor Antagonists01:27

Chemotherapy-Induced Nausea and Vomiting: 5-HT3 Receptor Antagonists

5-HT3 receptor antagonists, such as dolasetron, granisetron (Kytril), ondansetron (Zofran), and palonosetron (Axoli), are crucial in managing chemotherapy-induced nausea and vomiting (CINV) and postoperative nausea. These drugs selectively block 5-HT3 receptors in the visceral vagal and spinal afferent nerves, chemoreceptor trigger zone, and the vomiting center. They have a rapid onset of action and can be given as a single dose before chemotherapy. Ondansetron and granisetron, in particular,...
321
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
DNA Damage can Stall the Cell Cycle02:37

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
9.3K
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