Cancer therapy: Attempt cure or manage drug resistance?

Abstract

Cancer treatment is often aimed at achieving rapid, large, and sustained reductions in tumor burden. Even when these strong responses are achieved, treatment frequently fails due to the emergence of drug-resistant cell lineages. Over the last decade, a variety of authors have suggested that treatment should instead be aimed at containing resistance rather than curing the patient. That new philosophy poses a dilemma: how to choose between treatment regimens that can sometimes cure the patient and regimens that can delay progression but not cure the patient? Here, we investigate that choice. We define aspects of the evolution and ecology of tumor dynamics that determine whether it is better to attempt cure or to manage resistance. Even when it is possible to manage resistance and delay progression, this may not be the best treatment option. We show that the best option depends on how “cure” and “delaying progression” are prioritized, and how those priorities will vary among patients. We also discuss the difficulties of comparing in clinical trials traditional strategies that can sometimes successfully cure to alternative approaches where cure is not possible. More generally, where resistance management is possible, there are new challenges in communicating options to patients, setting treatment guidelines, and evaluating data from clinical trials.