biostudies-literatureGatenby RAEuropean Union's Horizon 2020 research and innovation programNCI NIH HHSNIH NCI3174-3177https://www.ebi.ac.uk/biostudies/studies/S-EPMC6606376biostudies-literatureUnknown79(13)While clinical cancer research has produced many highly effective drugs, the diversity and evolutionary capacity of most cancer populations remain insurmountable barriers to cure. Here, we propose that curative outcomes may, nevertheless, be achieved by sequencing therapies that are individually effective but noncurative. Basic principles for such an approach are derived from the eco-evolutionary dynamics of background extinctions in which a "first strike" reduces the size and heterogeneity of the population. When followed immediately by demographic and ecological "second strikes," the population can be reduced below some minimum threshold, leading inevitably to extinction. This strategy bears strong similarity to the empirically-derived curative therapy in childhood acute lymphocytic leukemia.Cancer researchFirst Strike-Second Strike Strategies in Metastatic Cancer: Lessons from the Evolutionary Dynamics of Extinction.PMC6606376R01 CA170595R01CA170595U54 CA193489690817U54 CA143970Zhang JGatenby RABrown JSfalseFirst Strike-Second Strike Strategies in Metastatic Cancer: Lessons from the Evolutionary Dynamics of Extinction.While clinical cancer research has produced many highly effective drugs, the diversity and evolutionary capacity of most cancer populations remain insurmountable barriers to cure. Here, we propose that curative outcomes may, nevertheless, be achieved by sequencing therapies that are individually effective but noncurative. Basic principles for such an approach are derived from the eco-evolutionary dynamics of background extinctions in which a "first strike" reduces the size and heterogeneity of the population. When followed immediately by demographic and ecological "second strikes," the population can be reduced below some minimum threshold, leading inevitably to extinction. This strategy bears strong similarity to the empirically-derived curative therapy in childhood acute lymphocytic leukemia.2019-01-01T00:00:00Z2019 Jul2024-11-08T22:13:05.962Z2020-07-04T07:16:23ZS-EPMC66063763122182110.1158/0008-5472.CAN-19-080710.1158/0008-5472.can-19-0807