Related Experiment Video
Updated: Jan 17, 2026
Author Spotlight: Genetic Profiling for Fluorouracil Response in Gastric Cancer
Published on: May 10, 2024
PARP inhibitors in gastric cancer: unlocking precision oncology
Derek Tai1, Vitor Goes2, Sharanya Kumar3
1Department of Internal Medicine, Loma Linda University Medical Center, Loma Linda, CA 92354, United States.
Abstract:
Gastric cancer (GC) demonstrates frequent alterations in homologous recombination repair (HRR) genes, and preclinical studies have demonstrated a clear synthetic lethality between HRR deficiency (HRD) and PARPi. While such preclinical synthetic lethality has translated into clinical benefits of PARPi in patients with HRD breast, ovarian, pancreatic, or prostate cancer, the therapeutic role of PARPi in GC remains unclear due to molecular heterogeneity and lack of validated biomarkers for patient selection. This review summarizes the mechanistic foundation for PARPi sensitivity in HRR-deficient GC tumors and evaluates emerging biomarkers, including genomic instability scores, RAD51 foci formation, mutational signatures, and candidate genes such as BRCA1/2, PALB2, and BARD1. We highlight key clinical trials and ongoing research aimed at refining patient selection, optimizing combination strategies, and identifying predictive biomarkers. Improving biomarkers to identify bona fide HRD is essential to optimizing PARPi as a valuable treatment option for patients with GC. We outline a pathway for biomarker-guided adoption of PARPi in GC management. Early-phase clinical trials of PARPi monotherapy in GC have yielded limited efficacy, likely due to variable HRD status and other mechanisms of primary resistance. Combining PARPi with chemotherapy, immune checkpoint inhibitors, or anti-angiogenic agents offers strategies to potentially increase the tumor susceptibility to PARPi and overcome resistance.
Insights
PARP inhibitors show promise for gastric cancer (GC) with homologous recombination deficiency (HRD). Improved biomarkers are crucial for selecting patients and optimizing PARP inhibitor therapy in GC treatment.
Area of Science:
- Oncology
- Genetics
- Pharmacology
Background:
- Gastric cancer (GC) frequently exhibits alterations in homologous recombination repair (HRR) genes.
- Preclinical data suggest synthetic lethality between HRR deficiency (HRD) and PARP inhibitors (PARPi).
- Clinical success of PARPi in other HRD cancers contrasts with unclear efficacy in GC due to heterogeneity and biomarker limitations.
Purpose of the Study:
- To review the mechanistic basis for PARPi sensitivity in HRR-deficient GC.
- To evaluate emerging biomarkers for patient selection in GC.
- To outline a strategy for biomarker-guided PARPi adoption in GC management.
Main Methods:
- Literature review of mechanistic studies, clinical trials, and biomarker research.
- Evaluation of genomic instability scores, RAD51 foci, mutational signatures, and candidate HRR genes (e.g., BRCA1/2, PALB2, BARD1).
- Analysis of strategies for patient selection and combination therapies.
Main Results:
- Early PARPi monotherapy trials in GC showed limited efficacy, likely due to variable HRD and resistance mechanisms.
- Biomarkers like genomic instability, RAD51 foci, and specific gene mutations are under investigation.
- Combination strategies (chemotherapy, immunotherapy, anti-angiogenics) may enhance PARPi effectiveness.
Conclusions:
- Accurate identification of HRD is essential for optimizing PARPi therapy in GC.
- Biomarker-guided approaches are needed to improve patient selection and treatment outcomes.
- Combination therapies represent a promising avenue to overcome resistance and enhance PARPi efficacy in GC.
More Related Videos
10:28Gene Regulation and Targeted Therapy in Gastric Cancer Peritoneal Metastasis: Radiological Findings from Dual Energy CT and PET/CT
Published on: January 22, 2018
08:59Looking 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
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:50Combination Therapies and Personalized Medicine
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...