SMT and TOFT: Why and How They are Opposite and Incompatible Paradigms.
The Somatic Mutation Theory (SMT) has been challenged on its fundamentals by the Tissue Organization Field Theory of Carcinogenesis (TOFT). However, a recent publication has questioned whether TOFT could be a valid alternative theory of carcinogenesis to that presented by SMT. Herein we critically review arguments supporting the irreducible opposition between the two theoretical approaches by highlighting differences regarding the philosophical, methodological and experimental approaches on which they respectively rely. We conclude that SMT has not explained carcinogenesis due to severe epistemological and empirical shortcomings, while TOFT is gaining momentum. The main issue is actually to submit SMT to rigorous testing. This concern includes the imperatives to seek evidence for disproving one's hypothesis, and to consider the whole, and not just selective evidence.
Department of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161, Rome, Italy. mariano.bizzarri@uniroma1.it.|Systems Biology Group Lab, Sapienza University of Rome, Via Antonio Scarpa 14, 00161, Rome, Italy. mariano.bizzarri@uniroma1.it.
Mariano
M
Bizzarri
Department of Surgery "Pietro Valdoni", Sapienza University of Rome, Via A. Scarpa 14, 00161, Rome, Italy.|Azienda Policlinico Umberto I, Viale del Policlinico 155, 00161, Rome, Italy.
Alessandra
A
Cucina
D000465:Algorithms; D063646:Carcinogenesis / Q000235:genetics*; D006801:Humans; D008954:Models, Biological; D009154:Mutation / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics*
D009363:Neoplasm Proteins
Oncogene; Reductionism; SMT; Systems biology; TOFT; Tumor microenvironment