Plasticity in Cancer Cell Populations: Biology, Mathematics and Philosophy of Cancer

Abstract

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Many Faces of Regulatory T Cells: Heterogeneity or Plasticity?

“…At this time, cells can switch their functions, phenotype and/or composition [18]. Regardless of stem cells, cellular plasticity is observed and is being intensively studied in tumors, where phenotype switching is a key contributor to therapy evasion [16]. A good example is the epithelial-to-mesenchymal transition (EMT) in response to microenvironmental stress.…”

“…If the former is the case, we can refer to cellular heterogeneity driven by changes in the genome and transcriptome, resulting in the emergence of distinct cell progenitors [14,15]. The second case is intrinsically related to cellular plasticity, which defines the ability of cells to change their phenotype in response to external stimuli without genetic mutations [16].…”

Mathematical Modelling of Cancer Growth and Drug Treatments: Taking Into Account Cell Population Heterogeneity and Plasticity

“…This certainly concerns genetic heterogeneity, i.e., situations in which spontaneous mutations have appeared due to the genetic instability of tumour cells, but isogenic heterogeneity resulting from nongenetic instabilities in gene expression due to the lability of epigenetic enzyme activity [53] is as much important [19], [20], [38], and it occurs before mutations, that remain rare events. The plasticity of cancer cells with respect to the expression of genes [12], [19], [38], [60], as all differentiations, that make an isogenic multicellular organism so varied in cell types (20 for sponges [41], [42], about 200 for human beings) is due to epigenetic factors. These are strictly controlled at the organismic level in physiology, and out of control in cancer [19], [20].…”

“…A recently autonomised field of knowledge, the so-called philosophy of cancer [4], [12], [55] considers cancer as an impairment of organismic control on both proliferation and differentiations [4]. It should be stressed that cancer is a disease that can be met only in the animal kingdom, constituted of multicellular organisms, that, different from plants (plants may also develop tumours, but they remain localised in capsules, never threatening the existence of the organism), are endowed with other properties such as motility and heterotrophy.…”

Improving cancer treatments via dynamical biophysical models

“…Relying on theoretical considerations, suggested by philosophers of science [2,45,46], it has recently been proposed that plasticity in cancer arises due to an anatomically localized loss of control of cell differentiation. This should result from impairments of mechanisms of maintenance of tissue cohesion and functional coherence, that themselves rely on intercellular signaling pathways and can be regarded as part of the immune system [47,48]. Moreover, maintenance of a differentiated cell status -at the level of a growing cell population, when differentiation occurs at asymmetrical mitoses -requires much energy for the activity of epigenetic enzymes.…”