The tissue organization field theory of cancer: A testable replacement for the somatic mutation theory

Abstract

The somatic mutation theory (SMT) of cancer has been and remains the prevalent theory attempting to explain how neoplasms arise and progress. This theory proposes that cancer is a clonal, cell-based disease, and implicitly assumes that quiescence is the default state of cells in multicellular organisms. The SMT has not been rigorously tested, and several lines of evidence raise questions that are not addressed by this theory. Herein, we propose experimental strategies that may validate the SMT. We also call attention to an alternative theory of carcinogenesis, the tissue organization field theory (TOFT), which posits that cancer is a tissue-based disease and that proliferation is the default state of all cells. Based on epistemological and experimental evidence, we argue that the TOFT compellingly explains carcinogenesis, while placing it within an evolutionarily relevant context.

Host epithelial geometry regulates breast cancer cell invasiveness

“…Our results show that the mechanical properties of the normal host epithelium may be critical for suppressing tumorigenic phenotype in cells with a tumorigenic genotype. These differences in tumor cell behavior depending on location within the host epithelium strengthen the importance of studying tumorigenesis in the context of a tissue rather than in isolated individual cells (9) and reinforce the importance of using 3D culture models to recapitulate the natural architecture of tissues and complement studies in vivo (59).…”

“…Moreover, the specific location where a tumor develops in the breast can have a profound effect on the resulting breast cancer outcome: patients with tumors in the upper lateral quadrant of the breast have a better prognosis than those with tumors that develop in one of the other three quadrants (6,7). These architecture-dependent variations in tumor development underscore the notion that the microenvironment of the tumor in vivo plays an important role in determining the phenotypic outcome of genetic mutations (8,9).…”

Le cancer et ses gènes insaisissables

“…La théorie du champ d'organisation tissulaire, quant à elle, en s'appuyant sur des fondements épistémologiques et empiriques, stipule que l'état par défaut de toutes les cellules est la prolifération et la motilité, ce qui est pertinent du point de vue de l'évolution, l'idée étant admise pour les organismes unicellulaires et pour les plantes. Dans ce cas, l'architecture altérée des tissus rend possible l'expression de l'état par défaut, et donc la croissance tumorale et les métastases [9,13]. L'inadéquation croissante entre la théorie des mutations somatiques et les faits empiriques a donc exigé l'ajout de corrections au fur et à mesure du temps à cette théorie.…”

“…Ce qui se produit au sein des cellules individuelles de la tumeur est donc une conséquence, et non une cause, de cette communication altérée entre les tissus. Selon la théorie du champ d'organisation tissulaire, les mutations repré-sentent un épiphénomène non pertinent du point de vue de la cancérogenèse et de sa progression [13,20].…”

Cancer: Escape route from a “doomed” host?

“…In May 2011 BioEssays published a paper arguing for the tissue organization field theory of cancer [3] (on which the above story also draws); several others addressing this, and related new ways of viewing cancer have followed [4,5,6,7]. Calls to view proliferation as the default state of cells, and the microenvironment and other epigenetic causes as the trigger for cancer will not disappear; might viewing cancer as a new species bring us yet further?…”