Competing views on cancer

Abstract

Despite intense research efforts that have provided enormous insight, cancer continues to be a poorly understood disease. There has been much debate over whether the cancerous state can be said to originate in a single cell or whether it is a reflection of aberrant behaviour on the part of a ‘society of cells’. This article presents, in the form of a debate conducted among the authors, three views of how the problem might be addressed. We do not claim that the views exhaust all possibilities. These views are (a) the tissue organization field theory (TOFT) that is based on a breakdown of tissue organization involving many cells from different embryological layers, (b) the cancer stem cell (CSC) hypothesis that focuses on genetic and epigenetic changes that take place within single cells, and (c) the proposition that rewiring of the cell’s protein interaction networks mediated by intrinsically disordered proteins (IDPs) drives the tumorigenic process. The views are based on different philosophical approaches. In detail, they differ on some points and agree on others. It is left to the reader to decide whether one approach to understanding cancer appears more promising than the other.

Pan-cancer methylation and expression profiling of adenocarcinomas revealed epigenetic silencing in the WNT signaling pathway

“…These genes were significantly enriched in developmental processes ( Figure 1D), implicating the importance of epigenetic repression of certain developmental programs in tumorigenesis. While somatic mutations have been widely considered as main drivers of tumors, amounting evidence has suggested that tumorigenesis is largely affected by surrounding environments and driven by aberrant epigenetic regulation during development [10,11] Our results provided supporting evidence that epigenetic aberration in development may be associated with adenocarcinoma.…”

Cancer as a disorder of patterning information: computational and biophysical perspectives on the cancer problem

“…A competing perspective is that of cancer as a circuit disease-a disorder of the complex biophysical, transcriptional, and epigenetic dynamics that regulate cellular state and the ability of cells to cooperate in vivo [6][7][8]. Under this view (sometimes called the tissue organization field theory or TOFT, [9,10]), cancer is akin to a traffic jam [11]-the problem is not a permanent discrete alteration within a founder cell and all of its clonal descendants, but an undesirable stable attractor in the complex network of controls that normally guides anatomical homeostasis [12].The relative merits of the two models have been discussed extensively [10,[13][14][15][16][17] …”

SMT and TOFT: Why and How They are Opposite and Incompatible Paradigms

“…Currently, SMT and TOFT are recognized to be different paradigms by independent researchers (Wolkenhauer and Green 2013;D'Anselmi et al 2011;Sonnenschein et al 2014b;Satgé and Bénard 2008;Prehn 2005;Schwartz et al2002;Baker et al 2010;Laforge et al 2005;Longo and Montévil 2014;Levin 2012;Smythies 2015;Tarin 2011).…”