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

Se Jin Oh1,2, Ji Yeon Lim1,3, Min Kyu Son1,2

  • 1BK21 Graduate Program, Department of Biomedical Sciences, Korea University College of Medicine, Seoul, 02841, Republic of Korea.

Nature Communications
|May 10, 2023
PubMed

Insights

Cisplatin resistance and neuropathic pain are linked to EGFR hyperactivation, driven by NANOG and TRPV1. Targeting TRPV1 may overcome resistance and alleviate pain in resistant cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pain Research

Background:

  • Cisplatin resistance and chemotherapy-induced neuropathic pain are significant clinical challenges.
  • Identifying novel therapeutic targets is crucial for improving cancer treatment outcomes.

Purpose of the Study:

  • To elucidate the molecular mechanisms linking cisplatin resistance, EGFR hyperactivation, and pain pathways.
  • To investigate the therapeutic potential of targeting TRPV1 in cisplatin-resistant cancers.

Main Methods:

  • Investigated the association between cisplatin resistance and EGFR hyperactivation.
  • Examined the role of NANOG and TRPV1 in EGFR activation and EGF secretion.
  • Assessed the effect of TRPV1 inhibition on cisplatin sensitivity and pain signaling.

Main Results:

  • Cisplatin resistance is strongly correlated with epidermal growth factor receptor (EGFR) hyperactivation.
  • NANOG upregulates the transient receptor potential vanilloid 1 (TRPV1), a pain channel.
  • TRPV1 promotes autophagy-mediated EGF secretion, activating EGFR-AKT signaling and conferring cisplatin resistance.
  • TRPV1 inhibition restores cisplatin sensitivity and may alleviate pain.

Conclusions:

  • A novel link exists between cisplatin resistance, EGFR hyperactivation, and TRPV1-mediated autocrine signaling.
  • TRPV1 is a potential therapeutic target to overcome cisplatin resistance and manage neuropathic pain in NANOG-positive cancers.

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