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Non-genetic mechanisms of therapeutic resistance in cancer

Jean-Christophe Marine1,2, Sarah-Jane Dawson3,4,5, Mark A Dawson6,7,8

  • 1Laboratory for Molecular Cancer Biology, VIB Center for Cancer Biology, KU Leuven, Leuven, Belgium. jeanchristophe.marine@kuleuven.vib.be.

Nature Reviews. Cancer
|October 9, 2020
PubMed

Insights

Cancer cells develop non-genetic adaptive mechanisms to resist therapy, challenging traditional views of genetic evolution. Innovative strategies are needed to monitor and counteract these diverse resistance pathways for better cancer treatment outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Therapeutic resistance remains a major obstacle in achieving curative cancer treatment.
  • Recent findings highlight non-genetic adaptive mechanisms as key drivers of acquired treatment resistance, complementing genetic evolution.
  • The interplay between a tumor's genetic landscape and non-genetic resistance strategies is increasingly recognized.

Purpose of the Study:

  • To discuss the fundamental principles of non-genetic therapy resistance in cancer.
  • To provide an overview of emerging data on non-genetic resistance pathways from clinical studies and advanced cancer models.
  • To highlight potential therapeutic strategies to overcome non-genetic adaptive resistance.

Main Methods:

  • Review of current clinical and experimental data on non-genetic resistance mechanisms.
  • Analysis of sophisticated cancer models investigating adaptive resistance pathways.
  • Perspective on emerging therapeutic avenues targeting non-genetic resistance.

Main Results:

  • Non-genetic adaptive mechanisms, including transcriptional, metabolic, and plasticity-driven changes (lineage switching, immune evasion), are crucial for cancer therapy resistance.
  • Oncogenic mutations can facilitate rapid adaptation or confer inherent cellular plasticity to evade therapy.
  • Diverse non-genetic resistance pathways present significant challenges for current cancer treatments.

Conclusions:

  • Understanding non-genetic resistance is critical for developing effective cancer therapies.
  • Innovative strategies are required to monitor and counteract non-genetic adaptive processes.
  • Targeting these non-genetic pathways offers promising avenues for overcoming therapeutic resistance and improving patient outcomes.

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