Distinct - but not mutually exclusive - hypotheses are proposed to explain
how established cancers progress in patients. Accounting for the phenotypic
heterogeneity frequently apparent within malignant tumors, these models are
based on the nature and reversibility of molecular changes that
drive disease progression. Using highly efficient xenograft assays, we have
tested the relevance of different models of cancer progression to human
melanoma. These studies reveal a remarkably dynamic inner world of melanoma
tumors characterized by extensive evolutionary change of some tumor genomes
and epigenomes during disease progression. The implications are profound of
these observations for developing treatment approaches that provide lasting
clinical benefit for patients with metastatic cancer.