Carcinogenesis Marked by Initiation

Abstract

My last installment in this debate1 focused on the carcinogenesis process as a whole to demonstrate the numerous environmental and physiological factors involved in the multistep processes of carcinogenesis, including the involvement of both somatic mutation and tissue environment dynamics (i.e., Somatic Mutation Theory (SMT) and Tissue Organization Field Theory (TOFT)). In this article, the focus will be primarily in the initiation of carcinogenesis, the all-consuming first step, when the novice cell makes a Faustian bargain2 with the Devil and enters the first of nine circles of Hell.3 Although, there is nothing comedic about the nine prominent changes that have thus far been identified for the development of a malignant tumor.4 The first step is the formation of the initiated cell. By definition, the initiated cell is irreversible due to a newly formed, fixed mutation that is oncogenic. The premise that the origin of the initiated cell occurs by the development of a fixed oncogenic mutation is well founded by a plethora of scientific evidence based mostly on genotoxic studies of chemical and physical carcinogens. The scientific evidence today suggests that the causes and definition of what constitute an initiated cell require updating. Regardless, the formation of the initiated cell is the first (so far) definable step in the pathway of cancer development. Initiation is a process of carcinogenesis that may well be neither the exclusive domain of either SMT or TOFT, but may offer both theories mechanisms on which to expound.