Systems biology of cancer: entropy, disorder, and selection-driven evolution to independence, invasion and "swarm intelligence"

Abstract

Our knowledge of the biology of solid cancer has greatly progressed during the last few years, and many excellent reviews dealing with the various aspects of this biology have appeared. In the present review, we attempt to bring together these subjects in a general systems biology narrative. It starts from the roles of what we term entropy of signaling and noise in the initial oncogenic events, to the first major transition of tumorigenesis: the independence of the tumor cell and the switch in its physiology, i.e., from subservience to the organism to its own independent Darwinian evolution. The development after independence involves a constant dynamic reprogramming of the cells and the emergence of a sort of collective intelligence leading to invasion and metastasis and seldom to the ultimate acquisition of immortality through inter-individual infection. At each step, the probability of success is minimal to infinitesimal, but the number of cells possibly involved and the time scale account for the relatively high occurrence of tumorigenesis and metastasis in multicellular organisms.

Fig. 1

The two extreme cases in the carcinogenetic transformation of a normal cell. Left: stepwise model in which sequential additional genetic events progressively lead to the fully developed, proliferative, and undifferentiated cancer cell (Vogelstein model). Right: catastrophic model in which a mitotic catastrophe (chromothripsis) or widespread mutations around a DNA repair site (kataegis) leads in one step to death of most cells and in one or a few cells to a cancer cell genotype. The two models might sequentially happen in the cells

Fig. 2

The first phase of progressive transformation of an epithelium to an independent tumor: loss of proliferation constrains and loss of tissue constrains in any order

Fig. 3

Schematic view of steps in tumor evolution. From one normal cell, to dominance of this cell, independent benign tumor, invasive tumor, cancer, and metastasis. The width of the arrows suggests the relative importance of the relations