title: Carcinogenesis explained within the context of a theory of organisms.
abstract: For a century, the somatic mutation theory (SMT) has been the prevalent theory to explain carcinogenesis. According to the SMT, cancer is a cellular problem, and thus, the level of organization where it should be studied is the cellular level. Additionally, the SMT proposes that cancer is a problem of the control of cell proliferation and assumes that proliferative quiescence is the default state of cells in metazoa. In 1999, a competing theory, the tissue organization field theory (TOFT), was proposed. In contraposition to the SMT, the TOFT posits that cancer is a tissue-based disease whereby carcinogens (directly) and mutations in the germ-line (indirectly) alter the normal interactions between the diverse components of an organ, such as the stroma and its adjacent epithelium. The TOFT explicitly acknowledges that the default state of all cells is proliferation with variation and motility. When taking into consideration the principle of organization, we posit that carcinogenesis can be explained as a relational problem whereby release of the constraints created by cell interactions and the physical forces generated by cellular agency lead cells within a tissue to regain their default state of proliferation with variation and motility. Within this perspective, what matters both in morphogenesis and carcinogenesis is not only molecules, but also biophysical forces generated by cells and tissues. Herein, we describe how the principles for a theory of organisms apply to the TOFT and thus to the study of carcinogenesis.
authors: Centre Cavaillès, École Normale Supérieure, Paris, France; Institut d'Etudes Avancees de Nantes, France; Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine, Boston, MA, USA. Electronic address: carlos.sonnenschein@tufts.edu.
authors: Carlos
authors: C
authors: Sonnenschein
authors: Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine, Boston, MA, USA; Centre Cavaillès, République des Savoirs, CNRS USR3608, Collège de France et Ecole Normale Supérieure, Paris, France. Electronic address: ana.soto@tufts.edu.
authors: Ana M
authors: AM
authors: Soto
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000139:chemically induced; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000139:chemically induced / Q000145:classification / Q000473:pathology*
keywords: Closure; Default state; Organicism; Stroma epithelium interactions; Tissue organization field theory