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[Cell signaling and CDDP resistance]

N Masumoto1, S Nakano

  • 1Dept. of Internal Medicine, Kyushu University, Faculty of Medicine.

Gan to Kagaku Ryoho. Cancer & Chemotherapy
|February 1, 1997
PubMed
Summary

The v-src oncogene confers resistance to Cisplatin (CDDP) chemotherapy by altering DNA repair pathways. Targeting intracellular signaling pathways may reverse this drug resistance in cancer treatment.

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Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genetics

Context:

  • Intracellular signaling pathways involving oncogenes are implicated in anticancer drug resistance.
  • The precise mechanisms underlying oncogene-induced drug resistance require further elucidation.
  • Human epithelial models are crucial for studying cancer development and drug response.

Purpose:

  • To investigate the role of specific oncogenes, v-src and ras, in mediating resistance to Cisplatin (CDDP).
  • To determine the molecular mechanisms by which oncogenes influence drug sensitivity and DNA repair.
  • To explore the potential of targeting intracellular signaling for overcoming anticancer drug resistance.

Summary:

  • Transfection of HAG-1 cells with the v-src oncogene, but not the activated ras oncogene, induced a neoplastic phenotype and resistance to Cisplatin (CDDP).
  • Src-transfected cells exhibited reduced formation of CDDP-induced DNA interstrand cross-links and accelerated DNA repair.
  • Inhibition of src kinase activity diminished CDDP resistance and DNA repair rates in src-transformed cells, suggesting v-src modulates DNA repair pathways.

Impact:

  • These findings highlight the v-src oncogene's role in conferring Cisplatin resistance through modulation of DNA repair mechanisms.
  • The study suggests that intracellular signaling pathways, particularly those involving protein tyrosine kinases like v-src, are viable targets for reversing anticancer drug resistance.
  • Understanding oncogene-driven resistance mechanisms can inform the development of novel therapeutic strategies to enhance chemotherapy efficacy.

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