Adaptation and selection during residual disease and tumor recurrence
Tumor recurrence following therapy is the leading cause of death in many cancer types, including some of the most common epithelial tumors such as breast and prostate cancer. Many breast tumors recur more than 5 years after initial surgery and treatment, and recurrences as long as 20 years following therapy have been documented. This has led to the suggestion that a population of tumor cells - referred to as minimal residual disease - can survive treatment and persist in a dormant, clinically undetectable state for years or even decades. These dormant residual cells are the likely reservoir for disease recurrence. Because recurrent breast cancer is generally incurable, developing strategies to forestall recurrence by therapeutically targeting residual cells during the dormant stage is of paramount importance. While recent work in this area has focused on specific pathways that promote the survival and recurrence of dormant cells, several fundamental questions about dormancy have not yet been addressed: How does the clonal composition of tumors change during dormancy and recurrence? Is tumor recurrence driven by the selection of a subset of dormant residual cells? Do dormant tumor cells undergo adaptive changes that allow them to recur? Because primary breast tumors are be heterogeneous, harboring different subclones of (epi)genetically distinct cells, it is likely that dormancy and recurrence are accompanied by profound changes in the...(see website for rest of abstract).