First 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.