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7355443 
Journal Article 
Review 
Integrating evolutionary dynamics into cancer therapy 
Gatenby, RA; Brown, JS 
2020 
1 
Nature Reviews. Clinical Oncology
ISSN: 1759-4774
EISSN: 1759-4782 
17 
11 
675-686 
English 
32699310 
WOS:000551360100001 
Many effective drugs for metastatic and/or advanced-stage cancers have been developed over the past decade, although the evolution of resistance remains the major barrier to disease control or cure. In large, diverse populations such as the cells that compose metastatic cancers, the emergence of cells that are resistant or that can quickly develop resistance is virtually inevitable and most likely cannot be prevented. However, clinically significant resistance occurs only when the pre-existing resistant phenotypes are able to proliferate extensively, a process governed by eco-evolutionary dynamics. Attempts to disrupt the molecular mechanisms of resistance have generally been unsuccessful in clinical practice. In this Review, we focus on the Darwinian processes driving the eco-evolutionary dynamics of treatment-resistant cancer populations. We describe a variety of evolutionarily informed strategies designed to increase the probability of disease control or cure by anticipating and steering the evolutionary dynamics of acquired resistance.