Synthetic lethality targets in pancreatic ductal adenocarcinoma: prevalence and limitations of liquid biopsy detection in a minority-serving cancer center.

Mahmoud Abdelsamia, Yafang Li, Daniel Eastwood, Ian Rabinowitz

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Article in Future oncology (London, England), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

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4 authors.

Mahmoud AbdelsamiaDivision of Hematology/Oncology, Department of Internal Medicine, University of New Mexico, Albuquerque, NM, USA.ORCID 0009-0006-8712-5579

Yafang LiDivision of Epidemiology, Biostatistics, and Preventive Medicine, University of New Mexico, Albuquerque, NM, USA.

Daniel EastwoodDivision of Epidemiology, Biostatistics, and Preventive Medicine, University of New Mexico, Albuquerque, NM, USA.

Ian RabinowitzDivision of Hematology/Oncology, Department of Internal Medicine, University of New Mexico, Albuquerque, NM, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimsSynthetic lethality (SL) exploits genetic vulnerabilities in cancer cells, offering therapeutic opportunities beyond conventional targets. While BRCA/poly(ADP-ribose) polymerase (PARP) inhibition is FDA-approved for pancreatic ductal adenocarcinoma (PDAC), the prevalence of other actionable SL targets remains poorly characterized. PATIENTS AND

methodsWe retrospectively analyzed 260 PDAC patients at the University of New Mexico Comprehensive Cancer Center (2017-2022); 74 underwent somatic sequencing (54 tissue, 17 liquid biopsy) and 117 underwent germline testing. The cohort included 11% Native American patients. We characterized eight SL gene targets and compared mutation detection between biopsy methods.

resultsTP53 mutations were identified in 73% of patients and CDKN2A was the most prevalent SL target (46%), followed by SMAD4 (24%), MTAP (15%), and ARID1A (14%). Liquid biopsy significantly underdetected key alterations: KRAS detection decreased from 93% (tissue) to 47% (liquid,

conclusionsMultiple SL targets beyond BRCA exist in PDAC. Liquid biopsy inadequately detects critical alterations, particularly deletions. Native American patients demonstrated preliminary molecular differences warranting validation in larger studies. Tissue-based molecular profiling will be essential for comprehensive patient selection as SL-targeted therapies advance.

Indexed as

Biomarkers, TumorCarcinoma, Pancreatic DuctalPancreatic NeoplasmsSynthetic Lethal MutationsAdultAgedAged, 80 and overCancer Care FacilitiesFemaleHumansLiquid BiopsyMaleMiddle AgedPrevalenceRetrospective StudiesSmad4 ProteinBiomarkers, TumorSmad4 ProteinSMAD4 protein, humanTumor Suppressor Protein p53CDKN2Aliquid biopsymolecular profilingNative AmericanPancreatic ductal adenocarcinomaPARP inhibitorsprecision oncologysynthetic lethality

Identifiers

PMID42422981

DOI10.1080/14796694.2026.2699426

PMCPMC13432814

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