Can a minimal replicating construct be identified as the embodiment of cancer?

Genomic instability is a hallmark of cancer. Cancer cells that exhibit abnormal chromosomes are characteristic of most advanced tumours, despite the potential threat represented by accumulated genetic damage. Carcinogenesis involves a loss of key components of the genetic and signalling molecular networks; hence some authors have suggested that this is part of a trend of cancer cells to behave as simple, minimal replicators. In this study, we explore this conjecture and suggest that, in the case of cancer, genomic instability has an upper limit that is associated with a minimal cancer cell network. Such a network would include (for a given microenvironment) the basic molecular components that allow cells to replicate and respond to selective pressures. However, it would also exhibit internal fragilities that could be exploited by appropriate therapies targeting the DNA repair machinery. The implications of this hypothesis are discussed. Cancer cells on the edge. As they evolve towards a genomically unstable state, cancer cells become capable of overcoming selection barriers. However, high instability might have a critical limit, with a minimal network of interacting genes required to sustain tumour survival, on the edge between order and disorder. © 2014 WILEY Periodicals, Inc.This work was supported by a grant MINECO, the Botin Foundation, and the Santa Fe Institute.Peer Reviewe