Background: Targeting the tumor microenvironment (TME) through which cancer stem cells
(CSCs) crosstalk for cancer initiation and progression, may open new treatments different from those
centered on the original hallmarks of cancer genetics thereby implying a new approach for suppression
of TME driven activation of CSCs. Cancer is dynamic, heterogeneous, evolving with the TME and can
be influenced by tissue-specific elasticity. One of the mediators and modulators of the crosstalk between
CSCs and mechanical forces is miRNA, which can be developmentally regulated, in a tissue- and cellspecific
Objective: Here, based on our previous data, we provide a framework through which such gene expression
changes in response to external mechanical forces can be understood during cancer progression.
Recognizing the ways mechanical forces regulate and affect intracellular signals with applications in
cancer stem cell biology. Such TME-targeted pathways shed new light on strategies for attacking cancer
stem cells with fewer side effects than traditional gene-based treatments for cancer, requiring a “watchand-
wait” approach. We attempt to address both normal brain microenvironment and tumor microenvironment
as both works together, intertwining in pathology and physiology – a balance that needs to be
maintained for the "watch-and-wait" approach to cancer.
Conclusion: This review connected the subjects of tissue elasticity, tumor microenvironment, epigenetic
of miRNAs, and stem-cell biology that are very relevant in cancer research and therapy. It attempts
to unify apparently separate entities in a complex biological web, network, and system in a realistic
and practical manner, i.e., to bridge basic research with clinical application.