Tumor and the Microenvironment: A Chance to Reframe the Paradigm of Carcinogenesis?

Abstract

The somatic mutation theory of carcinogenesis has eventually accumulated an impressive body of shortfalls and paradoxes, as admittedly claimed by its own supporters given that the cell-based approach can hardly explain the emergence of tissue-based processes, like cancer. However, experimental data and alternatives theories developed during the last decades may actually provide a new framework on which cancer research should be reframed. Such issue may be fulfilled embracing new theoretical perspectives, taking the cells-microenvironment interplay as the privileged level of observation and assuming radically different premises as well as new methodological frameworks. Within that perspective, the tumor microenvironment cannot be merely considered akin to new “factor” to be added to an already long list of “signaling factors”; microenvironment represents the physical-biochemical support of the morphogenetic field which drives epithelial cells towards differentiation and phenotype transformation, according to rules understandable only by means of a systems biology approach. That endeavour entails three fundamental aspects: general biological premises, the level of observation (i.e., the systems to which we are looking for), and the principles of biological organization that would help in integrating and understanding experimental data.

Potential use of microRNA-200c as a prognostic marker in non-small cell lung cancer

“…Genetic and epigenetic changes can occur at multiple levels, from chromothripsis or the loss or gain of entire chromosomes to a point mutation that alters a single DNA nucleotide, or to the silencing or activation of an miRNA that can alter the expression of up to 500 genes (25,26). To date, the mechanism through which miR-200c can affect the carcinogenic potential of cancer cells remains unknown and requires further elucidation at the molecular level.…”

The application of the fibroblast activation protein α-targeted immunotherapy strategy

“…The process of tumor invasion and metastasis is accompanied by angiogenesis and ECM degradation [39]. In most epithelial cancers greater than 1-2mm 3 in size, tumor progression is critically dependent on the supporting TME [40]. Previous studies in murine models have shown that vaccination against tumor vasculature in tumor stroma, results in tumor repression without significant adverse effects, suggesting that TME-targeted immunotherapy is likely to bring a benefit to cancer patients [41-43].…”

Stem Cell Differentiation Stage Factors from Zebrafish Embryo: A Novel Strategy to Modulate the Fate of Normal and Pathological Human (Stem) Cells

“…On the other hand, if we move from genomic alterations to cancer transcriptome, considered as “a whole”, as suggested by some authors, a more interesting picture emerges, from which it is possible observe a very great degree of order. In this vision tumors can be classified into a small number of discretely distinct groups, recording the organization of transcriptomes of cell types into groups of related tissues [51-54]. There are many studies that highlight the link between tumor malignancy and the presence of cancer stem cells [55] that seem to be resistant to conventional therapy, such as chemo- and radiotherapy.…”