Top: MRI scans of a patient with a primary glioblastoma before treatment, after initial gross total resection followed by chemo- and radiotherapy, and after tumor recurrence. Middle: A cartoon rendering of the associated changes in clonal populations in the tumor at each stage. Surgery successfully removes the tumor and eliminates many subclones. Postoperative chemo- and radiotherapies can further reduce tumor burden around the surgical cavity. However, a small fraction of tumor cells survive and initiate the formation of the recurrent tumor. The length of each line is proportional to the number of mutations acquired between each clone and branching indicates acquisition of divergent mutations. We have proposed calling these surviving cells recurrence-initiating stem-like cancer (RISC) cells. Bottom: Phylogenetic tree showing the process of clonal evolution in the primary tumor, the survival of RISC cells that have acquired adaptive resistance to therapy after initial treatments, and their evolution into a recurrent tumor. The length of each line is proportional to the number of mutations acquired between each clone, and branching indicates acquisition of divergent mutations.