Genome-wide CRISPR screen identifies AMBRA1 as a potential biomarker of response to platinum-based therapies in oral squamous cell carcinomas.

Authors

Lucía Acero-Riaguas, Iván López-García, Irene Posse-Alonso, Mariana Yáñez-Bartolomé, Alejandro San Lorenzo-Vaquero, Catalina Berca, César Pérez-Brotóns, Beatriz Castelo, Ana Sastre-Perona

Published in

iScience. Volume 29. Issue 8. Pages 116959. Aug 21, 2026. Epub Jul 27, 2026.

Abstract

Oral squamous cell carcinomas (OSCCs) are among the most frequent and lethal cancers worldwide. Advanced stage tumors are still treated with standard chemotherapy; however, most patients develop chemotherapy resistance. To uncover new functional biomarkers of cisplatin response, we performed a synthetic lethality genome-wide CRISPR-Cas9 screen in an OSCC cell line. This led to the discovery of AMBRA1 as a regulator of cisplatin sensitivity. In all tested OSCC cell lines and oral primary culture, AMBRA1 knockout cells showed increased sensitivity to cisplatin. Mechanistically, we demonstrated an unknown function of AMBRA1 in OSCCs, where loss of AMBRA1 led to an increase in S phase population, expression of genome instability markers, and DNA damage in basal conditions, predisposing cancer cells to an increased sensitivity to cisplatin and other platinum drugs. In summary, we uncovered AMBRA1 as a potential biomarker of response to platinum-based therapies in OSCCs.

PMID:
42548798
Bibliographic data and abstract were imported from PubMed on 04 Aug 2026.

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