Expression of Cytochrome P450 Enzymes in Pediatric Non-Rhabdomyosarcoma Soft Tissue Sarcomas: Possible Role in Carcinogenesis and Treatment Response

Int J Toxicol. 2022 May-Jun;41(3):234-242. doi: 10.1177/10915818221085909. Epub 2022 Apr 19.

Abstract

The 5-year relative survival rate estimate of treated patients with non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) is ∼50% since they generally present with tumor progression, relapse, metastasis, and/or chemoresistance. The expression of cytochrome P450 (CYP) enzymes in malignancies can affect the pharmacology of drugs commonly used in chemotherapy or confer susceptibility to development of chemical carcinogenesis; in addition, their specific tumor expression can be used as a therapeutic target. Using qPCR and Western blot assays, the expression of CYP1B1, CYP2E1, CYP3A4, and CYP3A5 were analyzed in a cohort of tumor tissue paired with non-malignant adjacent tissue of patients with NRSTS. The mRNA and protein expression of CYP1B1, CYP2E1, and CYP3A4 were significantly increased in tumor tissue. We propose that the expression of these isoforms is related to carcinogenesis and chemoresistance frequently observed in these neoplasms.

Keywords: chemoresistance; cytochrome P450; sarcoma; therapeutic target.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinogenesis
  • Child
  • Cytochrome P-450 CYP2E1 / metabolism
  • Cytochrome P-450 CYP3A* / genetics
  • Cytochrome P-450 Enzyme System / genetics
  • Cytochrome P-450 Enzyme System / metabolism
  • Humans
  • Sarcoma* / drug therapy
  • Sarcoma* / genetics
  • Sarcoma* / pathology

Substances

  • Cytochrome P-450 Enzyme System
  • Cytochrome P-450 CYP2E1
  • Cytochrome P-450 CYP3A