The current paradigm for cancer initiation and progression rests on the groundbreaking
discoveries of oncogenes and tumor suppressor genes. This framework has revealed much
about the role of genetic alterations in the underlying signaling pathways central to normal
cellular function and to tumor progression. However, it is clear that single gene theories or
even sequential acquisition of mutations underestimate the nature of the genetic and
epigenetic changes in tumors, and do not account for the observation that many cancer …