Media contributions
1Media contributions
Title Targeting DNA Repair Mechanisms: Exploiting Acquired Vulnerabilities to Overcome Resistance in Cholangiocarcinoma Media name/outlet Dojindo Country/Territory Japan Date 3/04/26 Description Current therapeutic strategies for Cholangiocarcinoma (CCA) are frequently constrained by the rapid onset of chemoresistance, rendering standard-of-care regimens like gemcitabine and cisplatin (GEM/CIS) ineffective over time. Recent advances in genomic profiling have revealed that CCA possesses a high frequency of alterations in DNA Damage Response (DDR) genes, providing a landscape for targeted intervention. This article explores the transition from traditional cytotoxic approaches to the strategic inhibition of DNA repair enzymes, such as PARP and ATR. We argue that the adaptive reprogramming of CCA cells during treatment creates specific acquired vulnerabilities — molecular dependencies that do not exist in drug-naïve cells. By mapping these resistance trajectories, our research demonstrates that combinations of PARP and ATR inhibitors can effectively exploit the genomic instability inherent in CCA. This approach transforms the challenge of drug resistance into a therapeutic opportunity, offering a blueprint for more durable and personalized clinical interventions. URL https://www.dojindo.co.jp/letterj/196/serialization/serialization01.html Persons Donniphat Dejsuphong, Rakkreat Wikiniyadhanee, Tassanee Lerksuthirat, Sermsiri Chitphuk