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Growth suppression of human oral cancer cells by candidate agents for cetuximab-side effects

Katsuhiro Uzawa1, Atsushi Kasamatsu2, Tomoaki Saito2

  • 1Department of Oral Science, Graduate School of Medicine, Chiba University, 1-8- 1 Inohana, Chuo-ku, Chiba 260-8670, Japan; Department of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, 1-8-1 Inohana, Chuo-ku, Chiba 260-8677, Japan.

Experimental Cell Research
|January 29, 2019
PubMed

Insights

Cetuximab treats oral cancer but causes skin rash and low magnesium. New research identifies potential therapies, flavagline and SB203580, to manage these side effects and enhance cancer treatment.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Cetuximab is a key treatment for oral squamous cell carcinoma (OSCC).
  • Cetuximab's common side effects include skin rash and hypomagnesemia, with poorly understood mechanisms.
  • Identifying therapeutic agents for these toxicities is crucial for patient management.

Purpose of the Study:

  • To investigate the molecular mechanisms underlying cetuximab-induced toxicities.
  • To identify potential therapeutic agents for managing cetuximab-related skin rash and hypomagnesemia.
  • To evaluate the efficacy of combining cetuximab with novel agents for OSCC treatment.

Main Methods:

  • Gene expression profiling was used to analyze cetuximab's effects on human skin (HaCaT) and embryonic kidney (HEK293) cells.
  • The p38 inhibitor SB203580 and flavagline were tested for their ability to counteract cetuximab's molecular effects.
  • In vivo studies assessed the combination therapy's effect on OSCC growth.

Main Results:

  • Cetuximab activated p38 MAPK pathways in skin cells and inhibited c-Fos-related signals in kidney cells.
  • SB203580 inhibited p38 MAPK targets, while flavagline reactivated c-Fos-related factors.
  • Flavagline showed an additive effect on OSCC growth inhibition in vivo without interfering with cetuximab's efficacy.

Conclusions:

  • SB203580 and flavagline show potential as therapeutic agents for cetuximab-related toxicities.
  • Flavagline may enhance cetuximab's anti-cancer effects in OSCC.
  • Combination therapy with cetuximab and these agents presents a promising strategy for OSCC patients.
Keywords:
Cetuximab side effectsFlavaglineSB203580TRPM6Tumor growth suppressionp38

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