Related Experiment Video

Updated: Sep 10, 2025

Chromogenic In Situ Hybridization as a Tool for HPV-Related Head and Neck Cancer Diagnosis
06:57

Chromogenic In Situ Hybridization as a Tool for HPV-Related Head and Neck Cancer Diagnosis

Published on: June 14, 2019

10.6K

Noncanonical Pathways of Proteasome Inhibition in HPV-Negative Head & Neck Cancer

Hye-Yeon Lee1, Ji-Yeong Kim1, Zhiyong Wang2

  • 1Department of Otorhinolaryngology-Head & Neck Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.

Molecular Carcinogenesis
|August 20, 2025
PubMed

Insights

Carfilzomib (CFZ) effectively inhibits head and neck cancer cell growth and induces apoptosis, particularly in HPV-negative HNSCC. This proteasome inhibitor shows promise in overcoming cisplatin resistance, suggesting a new therapeutic avenue.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Carfilzomib (CFZ) is a proteasome inhibitor used for multiple myeloma.
  • Its efficacy in head and neck squamous cell carcinoma (HNSCC), especially HPV-negative types, is not well-established.
  • Understanding CFZ's impact on HNSCC is crucial for developing new treatment strategies.

Purpose of the Study:

  • To evaluate the anticancer potential of carfilzomib (CFZ) in HPV-positive and HPV-negative head and neck cancer cells (HNSCC).
  • To investigate the mechanisms underlying CFZ's effects on HNSCC proliferation and apoptosis.
  • To assess CFZ's efficacy in overcoming cisplatin resistance in HPV-negative HNSCC.

Main Methods:

  • In vitro assessment of CFZ's IC50 in various HNSCC cell lines.
  • Analysis of signaling pathways (PI3K/AKT/mTOR, p21) affected by CFZ treatment.
  • In vivo evaluation of CFZ's effect on tumor growth in mice bearing xenografted HPV-negative HNSCC cells.

Main Results:

  • CFZ demonstrated significantly higher potency (lower IC50) in HPV-negative CAL-27 HNSCC cells compared to other HNSCC lines.
  • CFZ inhibited Akt/mTOR signaling (p-Akt, p-S6) and activated p21, leading to growth inhibition and apoptosis in CAL-27 cells.
  • CFZ treatment reduced tumor growth in mice with xenografted HPV-negative CAL-27 tumors.

Conclusions:

  • Carfilzomib induces cytotoxic effects in HNSCC, primarily through cell growth inhibition and apoptosis via the PI3K/AKT/mTOR and p21 pathways.
  • CFZ demonstrates potential as a therapeutic agent for HPV-negative HNSCC, offering a strategy to overcome cisplatin resistance.
Keywords:
HPV‐negative HNSCCPI3K/AKT/mTOR signaling pathwaycarfilzomibhead & neck cancerproteasome inhibitor

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