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The Genetic/Non-genetic Duality of Drug 'Resistance' in Cancer
Ravi Salgia1, Prakash Kulkarni1
1Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA 91010, USA.
Abstract:
Drug resistance is a serious impediment to the treatment of cancer. However, the mechanisms involved remain poorly understood. While it is widely held that the phenomenon is genetic in nature, emerging evidence suggests that non-genetic mechanisms may also be important. Furthermore, at least in some cases, refractoriness to treatment can be reversed by epigenetic reprogramming, and combination and intermittent therapies, as opposed to sustained monotherapy, appear more effective in attenuating it. Here we iterate the confusion in understanding the phenomenon by which cancer cells evade drug response and underscore the need to recognize the genetic/non-genetic duality of drug resistance in cancer. We discuss how ecological and evolutionary principles may help to reconcile the duality and may even offer new treatment strategies.
Insights
Cancer drug resistance, often assumed genetic, may also involve non-genetic factors. Understanding this duality is key to developing new, effective cancer treatment strategies.
Area of Science:
- Oncology
- Cancer Biology
- Evolutionary Biology
Background:
- Drug resistance is a major obstacle in cancer treatment.
- The underlying mechanisms of drug resistance are not fully understood.
- Genetic mechanisms are traditionally emphasized, but non-genetic factors are gaining recognition.
Purpose of the Study:
- To highlight the confusion surrounding cancer drug resistance mechanisms.
- To emphasize the need to consider both genetic and non-genetic aspects of drug resistance.
- To explore how ecological and evolutionary principles can inform cancer treatment strategies.
Main Methods:
- Literature review and conceptual synthesis.
- Discussion of emerging evidence on non-genetic resistance.
- Application of ecological and evolutionary principles to cancer resistance.
Main Results:
- Cancer drug resistance exhibits a duality, involving both genetic and non-genetic mechanisms.
- Epigenetic reprogramming can reverse treatment refractoriness in some cases.
- Combination and intermittent therapies show promise over sustained monotherapy.
Conclusions:
- Recognizing the genetic/non-genetic duality of cancer drug resistance is crucial.
- Ecological and evolutionary frameworks offer novel insights into resistance.
- These principles may lead to the development of improved cancer treatment strategies.