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Metabolic Plasticity in Melanoma Progression and Response to Oncogene Targeted Therapies

Arwa Alkaraki1,2, Grant A McArthur1,2, Karen E Sheppard1,2,3

  • 1Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia.

Cancers
|November 27, 2021
PubMed

Insights

Melanoma cells adapt to therapies through non-genetic changes in metabolism, hindering treatment. Understanding this metabolic plasticity is key to overcoming therapy resistance and preventing melanoma relapse.

Area of Science:

  • Oncology
  • Cancer Biology
  • Metabolic Research

Background:

  • Therapy resistance remains a significant obstacle in achieving curative treatments for melanoma.
  • Non-genetic adaptive mechanisms, including metabolic reprogramming, play a crucial role in melanoma therapy resistance and relapse.

Purpose of the Study:

  • To explore the role of melanoma's inherent metabolic plasticity in disease progression and therapy resistance.
  • To detail metabolic alterations during targeted therapy response phases (early response, drug tolerance, acquired resistance).
  • To discuss the influence of non-genetic programs like transcription and translation on these adaptive processes.

Main Methods:

  • Review of current clinical and experimental findings on melanoma metabolism.
  • Analysis of metabolic changes during different stages of targeted therapy response.
  • Examination of non-genetic regulatory mechanisms (transcription, translation) in therapy resistance.

Main Results:

  • Melanoma cells exhibit significant metabolic plasticity, altering their metabolism reversibly during metastasis and in response to anti-cancer therapies.
  • Metabolic reprogramming is a key driver of both melanoma progression and the development of resistance to targeted therapies.
  • Non-genetic adaptive mechanisms, controlled by transcriptional and translational programs, are prevalent and diverse.

Conclusions:

  • Melanoma's metabolic plasticity is a critical factor enabling disease progression and the acquisition of therapy resistance.
  • Innovative strategies are needed to monitor and counteract these adaptive, non-genetic resistance mechanisms to improve melanoma treatment outcomes.
Keywords:
melanomametabolismmetastasisplasticityresistancetargeted therapy

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