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Oncogene Overdose: Too Much of a Bad Thing for Oncogene-Addicted Cancer Cells

Amit Dipak Amin1, Soumya S Rajan2, Matthew J Groysman3

  • 1Department of Medicine, Division of Hematology-Oncology, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA.

Biomarkers in Cancer
|December 22, 2015
PubMed

Insights

Targeted cancer therapy resistance can be overcome by exploiting oncogene overexpression. Maintaining optimal oncogenic signaling levels, not too high or too low, is key for effective treatment and tumor control.

Area of Science:

  • Oncology
  • Cancer Therapeutics
  • Molecular Biology

Background:

  • Acquired resistance to targeted inhibitors is a significant challenge in treating oncogene-addicted cancers.
  • Current strategies like newer-generation inhibitors and combination therapies offer limited durable patient benefit.
  • Oncogene overexpression can emerge as a resistance mechanism.

Purpose of the Study:

  • To discuss the potential of exploiting oncogene overexpression as a therapeutic strategy.
  • To highlight the concept of 'oncogene overdose' and its implications in cancer treatment.
  • To explore novel approaches for overcoming resistance in oncogene-driven malignancies.

Main Methods:

  • Review of recent studies focusing on oncogene overexpression and resistance.
  • Discussion of specific examples including mutant-BRAF in melanoma and NPM-ALK in lymphoma.
  • Analysis of the concept of maintaining 'just-right' oncogenic signaling levels.

Main Results:

  • Oncogene overexpression can be a resistance mechanism, suggesting 'oncogene overdose' can be detrimental.
  • This 'oncogene overdose' phenomenon may be exploitable for therapeutic benefit.
  • Intermittent dosing strategies and pharmacological induction of oncogene overdose are potential applications.

Conclusions:

  • Exploiting oncogene overexpression represents a promising third approach to combatting cancer therapy resistance.
  • Understanding and manipulating oncogenic signaling levels is crucial for durable tumor control.
  • Further research into intermittent dosing and pharmacologically inducible oncogene overdose is warranted.
Keywords:
ALKBRAFintermittent dosingoncogene addictiononcogene overdosethe Goldilocks principle

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