AI Article Synopsis
- Cisplatin and gemcitabine are key chemotherapy drugs for treating solid tumors, but resistance to these drugs limits their effectiveness.
- The study identifies PAF1 as a significant factor in the resistance of ovarian, lung, and pancreatic cancers to these chemotherapeutics by enhancing DNA repair mechanisms.
- Targeting the interaction between PAF1 and RAD52, along with traditional treatments, could improve outcomes by reducing the survival of resistant cancer cells.
Article Abstract
Cisplatin- and gemcitabine-based chemotherapeutics represent a mainstay of cancer therapy for most solid tumors; however, resistance limits their curative potential. Here, we identify RNA polymerase II-associated factor 1 (PAF1) as a common driver of cisplatin and gemcitabine resistance in human cancers (ovarian, lung, and pancreas). Mechanistically, cisplatin- and gemcitabine-resistant cells show enhanced DNA repair, which is inhibited by PAF1 silencing. We demonstrate an increased interaction of PAF1 with RAD52 in resistant cells. Targeting the PAF1 and RAD52 axis combined with cisplatin or gemcitabine strongly diminishes the survival potential of resistant cells. Overall, this study shows clinical evidence that the expression of PAF1 contributes to chemotherapy resistance and worse clinical outcome for lethal cancers.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10374878 | PMC |
| http://dx.doi.org/10.1016/j.celrep.2023.112043 | DOI Listing |
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