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Papers of the Week

Papers: 6 May 2023 - 12 May 2023

Basic Science

Animal Studies, Genetics, Molecular/Cellular, Neurobiology, Pharmacology/Drug Development

Cancer Pain, Inflammation/Inflammatory, Neuropathic Pain

2023 May 10

Nat Commun




TRPV1 inhibition overcomes cisplatin resistance by blocking autophagy-mediated hyperactivation of EGFR signaling pathway.


Oh SJ, Lim JY, Son MK, Ahn JH, Song KH, Lee HJ, Kim S, Cho EH, Chung JY, Cho H, Kim H, Kim JH, Park J, Choi J, Hwang SW, Kim TW


Cisplatin resistance along with chemotherapy-induced neuropathic pain is an important cause of treatment failure for many cancer types and represents an unmet clinical need. Therefore, future studies should provide evidence regarding the mechanisms of potential targets that can overcome the resistance as well as alleviate pain. Here, we show that the emergence of cisplatin resistance is highly associated with EGFR hyperactivation, and that EGFR hyperactivation is arisen by a transcriptional increase in the pain-generating channel, TRPV1, via NANOG. Furthermore, TRPV1 promotes autophagy-mediated EGF secretion via Ca influx, which activates the EGFR-AKT signaling and, consequentially, the acquisition of cisplatin resistance. Importantly, TRPV1 inhibition renders tumors susceptible to cisplatin. Thus, our findings indicate a link among cisplatin resistance, EGFR hyperactivation, and TRPV1-mediated autophagic secretion, and implicate that TRPV1 could be a crucial drug target that could not only overcome cisplatin resistance but also alleviate pain in NANOG cisplatin-resistant cancer.