A CINful way to overcome addiction: how chromosomal instability enables cancer to overcome its oncogene addiction

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Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence
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Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence

Published on: January 7, 2019

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Daniel Bronder1,2, Samuel F Bakhoum3,4

  • 1Genetics Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD, USA.

EMBO Molecular Medicine
|February 20, 2020
PubMed

Insights

Chromosomal instability in cancer can create new oncogenic drivers, helping tumors resist targeted therapies. This genomic diversity acts as an adaptive survival mechanism against cancer treatments.

Area of Science:

  • Cancer Biology
  • Genetics
  • Oncology

Background:

  • Targeted therapies offer a therapeutic window for oncogene-addicted tumors but frequently face resistance.
  • Mechanisms of resistance, including target gene mutations, are well-documented.
  • The link between chromosomal instability and targeted therapy resistance is established but mechanistically unclear.

Discussion:

  • Salgueiro et al. demonstrate that chromosomal instability (CI) generates alternative oncogenic drivers.
  • This genomic diversification allows cancer cells to bypass the oncogene withdrawal bottleneck.
  • CI functions as an adaptive response to therapeutic pressure.

Key Insights:

  • Chromosomal instability fuels cancer evolution by creating new oncogenic drivers.
  • This process enables tumors to overcome targeted therapy-induced oncogene addiction.
  • Genomic diversity generated by CI is a key factor in therapeutic resistance.

Outlook:

  • Understanding CI's role in resistance can inform novel therapeutic strategies.
  • Targeting CI or its consequences may resensitize tumors to existing therapies.
  • Further research into CI-driven adaptive responses is crucial for improving cancer treatment outcomes.

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