A thermodynamic interpretation of malignancy: do the genes come later?

Abstract

Current theories on cancer development focus on ‘unlucky’ mutations affecting oncogenes or tumour suppressor genes. In this article a theory will be developed which interprets cancer as an adaptive phenomenon – a response to cellular stress induced by an energetic overload which would ultimately lead to an increase in cellular entropy. One of these adaptive mechanisms is paneuploid polyploidization, a phenomenon frequently described in malignant tumours. This inherent property of the genome to multiply with limited sequence variability may be involved just to make new proteins which are more appropriate to manage the harmful situation of energetic overload. Another important mechanism to prevent increasing entropy is the change in chirality of proteins and carbon hydrates because the use of enantiomers with higher intrinsic energy ultimately reduces entropy of the cell. These chiral alterations in turn affect the molecular structures of proteins and DNA, resulting in abnormal function of the former and disturbances of replication, transcription and repair of the latter. Moreover, the altered proteins may – as a secondary step – induce structural changes of the DNA. Because changes in chirality affect the structure of a cell randomly, one can expect alterations of multiple genes or proteins, and this is exactly what has been described in the literature. Therefore, this hypothesis may help to clarify confusing findings of tumour genetics accumulated over the last two decades. Cancer could be seen as a reaction of a cell to entrap energy which reduces entropy, or, in other words, cancer may best be regarded as entropic devolution.