{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T20:41:59Z","timestamp":1791492119854,"version":"4.3.4"},"reference-count":79,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T00:00:00Z","timestamp":1758067200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>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.<\/jats:p>","DOI":"10.1093\/oncolo\/oyaf283","type":"journal-article","created":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T23:18:18Z","timestamp":1758323898000},"source":"Crossref","is-referenced-by-count":7,"title":["PARP inhibitors in gastric cancer: unlocking precision oncology"],"prefix":"10.1093","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6461-5560","authenticated-orcid":false,"given":"Derek","family":"Tai","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Loma Linda University Medical Center , Loma Linda, CA 92354,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vitor","family":"Goes","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hospital Israelita Albert Einstein , S\u00e3o Paulo, SP 05652-900,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharanya","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Riverside University Health System , Moreno Valley, CA 92555,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pranati","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Loma Linda University Medical Center , Loma Linda, CA 92354,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farris","family":"Al-Manaseer","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Loma Linda University Medical Center , Loma Linda, CA 92354,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of California San Francisco Fresno , Fresno, CA 93701,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiana","family":"Crook","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology and Therapeutics Research, City of Hope , Duarte, CA 91010,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Guzman","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology and Therapeutics Research, City of Hope , Duarte, CA 91010,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3221-595X","authenticated-orcid":false,"given":"Xiaolin","family":"Zhu","sequence":"additional","affiliation":[{"name":"Helen Diller Family Comprehensive Cancer Center, University of California San Francisco , San Francisco, CA 94115,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5330-7522","authenticated-orcid":false,"given":"Daneng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology and Therapeutics Research, City of Hope , Duarte, CA 91010,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5762-6683","authenticated-orcid":false,"given":"Dani","family":"Castillo","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology and Therapeutics Research, City of Hope , Duarte, CA 91010,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,9,17]]},"reference":[{"key":"2025101709170427400_oyaf283-B1","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1038\/nm.3850","article-title":"Molecular analysis of gastric cancer identifies subtypes 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implications for prognosis and therapy","volume":"112","author":"Chen","year":"2015","journal-title":"Proc Natl Acad Sci USA"},{"key":"2025101709170427400_oyaf283-B5","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1038\/nature03443","article-title":"Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase","volume":"434","author":"Bryant","year":"2005","journal-title":"Nature"},{"key":"2025101709170427400_oyaf283-B6","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1038\/nature03445","article-title":"Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy","volume":"434","author":"Farmer","year":"2005","journal-title":"Nature"},{"key":"2025101709170427400_oyaf283-B7","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.dnarep.2018.08.021","article-title":"Mechanisms of PARP inhibitor sensitivity and resistance","volume":"71","author":"D\u2019Andrea","year":"2018","journal-title":"DNA Repair 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