Elevated PAF1-RAD52 axis confers chemoresistance to human cancers.

Authors :: Rauth S
Ganguly K
Atri P
Parte S
Nimmakayala RK
Varadharaj V
Nallasamy P
Vengoji R
Ogunleye AO
Lakshmanan I
Chirravuri R
Bessho M
Cox JL
Foster JM
Talmon GA
Bessho T
Ganti AK
Batra SK
Ponnusamy MP
Source :: Cell reports [Cell Rep] 2023 Feb 28; Vol. 42 (2), pp. 112043. Date of Electronic Publication: 2023 Jan 28.
Publication Year :: 2023
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.<br />Competing Interests: Declaration of interests S.K.B. is one of the co-founders of Sanguine Diagnostics and Therapeutics, Inc. The other authors declare no competing interests.<br /> (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)