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within normal, non-cancer tissues. However, our understanding of what constitutes tissue-specific micro-
environment conditions is still very incomplete. Also, it is highly likely that individuals will have their own
set of micro-environmental, chemical and biological conditions, so it will be necessary to analyze their tissue
microenvironments in considerable detail. Clearly, cells and tissues exist in complex three-dimensional en-
vironments, which include both extra- and intracellular environments. To analyze these microenvironments
[54]
new technologies are being developed, including atomic force microscopy , quantitative extracellular
[55]
[56]
matrix proteomics , and single cell multiomics that are being used to create complex databases of tissue
micro-environmental factors that will hopefully facilitate the identification of those significant factors that
allow for the selection of normal as opposed to cancer cells.

However, at first glance there appears to be the same underlying problem with this approach as the one that
has characterized attempts to analyze the genomic and post-genomic events that cause cells to become on-
cogenic. Namely, the inability to identify the critical oncogenic events involved because we can only measure
conditions before and after a cell becomes cancerous. However, the tissue micro-environmental conditions
that result in normal cells being selected do not suffer from this drawback, as normal cells remain dominant
in tissue over relatively long periods of time, presumably because they are subject to relatively consistent tis-
sue micro-environmental conditions. Nevertheless, it is important to note that tissue microenvironments
are likely to be highly individualized, so that even within an individual different tissue microenvironments
might exist around different tissues.

Conclusion
Before the discovery of ITGH and now CSGV, the novel approach to cancer treatment that we are suggesting
would have never been considered. However, if it is proven that cancer-associated genes within tumors as
well as normal tissue consistently exhibit CSGV. Then a treatment approach that includes the goal of rese-
lecting normal tissues by adjusting the tissue microenvironment, would seem to be the logical way to ensure
that cancer treatments finally result in the permanent elimination of cancer.

DECARATIONS
Authors’ contributions
Design: Gottlieb B
Literature research: Gottlieb B
Sequencing: Babrzadeh F, Wang C, Gharizadeh B
Analysis of data: Oros KK, Greenwood CMT
Tissue and DNA preparation: Alvarado C
Tumor samples: Basik M
Manuscript writing: Gottlieb B
Manuscript editing: Beitel LK, Trifiro M

Availability of data and materials
Data is available from Dr. Bruce Gottlieb. Materials are unavailable.

Financial support and sponsorship
This study was supported by a grant to BG from the Weekend to End Breast Cancer Fund of the Jewish Gen-
eral Hospital, Montreal, Quebec, Canada.

Conflicts of interest
All authors declare that there are no conflicts of interest.