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Mutant onco-proteins as drug targets: successes, failures, and future prospects

Frank McCormick1

  • 1Helen Diller Family Comprehensive Cancer Center, UCSF, 1450 3rd Street, Room 371, Box 0128, San Francisco, CA 94158, USA. mccormick@cc.ucsf.edu

Current Opinion in Genetics & Development
|January 18, 2011
PubMed

Insights

Targeting mutant onco-proteins shows promise in cancer treatment, but drug resistance is a major hurdle. New strategies like systemic RNA interference are needed for tumors driven by undruggable or multiple targets.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • Mutant onco-proteins are key drivers of cancer and attractive therapeutic targets.
  • Clinical success is often limited by the rapid development of drug resistance through various mechanisms.
  • Current treatment strategies face challenges with tumors driven by undruggable or multiple oncogenic drivers.

Purpose of the Study:

  • To evaluate the potential of targeting mutant onco-proteins in cancer therapy.
  • To address the challenge of acquired drug resistance in cancer treatment.
  • To explore novel therapeutic approaches for tumors with complex driver mutations.

Main Methods:

  • Review of clinical outcomes for targeted onco-protein therapies.
  • Analysis of mechanisms underlying drug resistance in cancer.
  • Assessment of systemic RNA interference as a potential therapeutic strategy.

Main Results:

  • Mutant onco-proteins are causally linked to cancer, validating them as drug targets.
  • Drug resistance frequently emerges, limiting clinical benefit.
  • The proportion of cancers dependent on single, druggable onco-proteins remains undetermined.
  • Many tumors are driven by undruggable or multiple oncogenic drivers, necessitating new therapeutic modalities.

Conclusions:

  • Targeting mutant onco-proteins is a validated strategy, but drug resistance necessitates further innovation.
  • Systemic RNA interference presents a promising avenue for overcoming resistance and treating complex cancers.
  • New therapeutic paradigms are required for the majority of tumors driven by undruggable or multiple oncogenic drivers.

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