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Role of oncogenes in resistance and killing by cancer therapeutic agents

W S el-Deiry1

  • 1Howard Hughes Medical Institute, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.

Current Opinion in Oncology
|January 1, 1997
PubMed

Insights

Chemotherapeutic drug resistance in cancer is a major challenge. This study reviews mechanisms like transporter proteins, detoxification enzymes, DNA repair, and oncogene activation, focusing on oncogenes and potential reversal strategies.

Area of Science:

  • Molecular Oncology
  • Cancer Biology
  • Drug Resistance Mechanisms

Background:

  • Chemotherapeutic drug resistance significantly hinders effective cancer therapy.
  • Understanding resistance mechanisms is crucial for developing improved cancer treatments.

Purpose of the Study:

  • To provide an overview of molecular mechanisms contributing to chemoresistance.
  • To highlight the specific role of oncogenes in drug resistance.
  • To discuss current strategies for overcoming chemoresistance.

Main Methods:

  • Literature review of molecular oncology and cancer resistance mechanisms.
  • Analysis of P-glycoprotein family transporters, detoxification proteins, DNA repair molecules, and oncogenes.
  • Discussion of therapeutic strategies targeting resistance pathways.

Main Results:

  • Chemoresistance involves multiple mechanisms including transporter overexpression (P-glycoprotein family), altered detoxification/activation enzymes, DNA repair defects, and oncogene activation.
  • Oncogenes such as Her-2/neu, bcl-2, and mutant p53 play a significant role in promoting chemoresistance.
  • Various strategies are being explored to reverse or circumvent these resistance mechanisms.

Conclusions:

  • Chemoresistance is a complex multifactorial process in cancer therapy.
  • Targeting oncogene-mediated resistance pathways offers promising therapeutic avenues.
  • Further research into resistance mechanisms is essential for advancing cancer treatment efficacy.

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