genesis of cancer appears to be a complex matter, which is not simply
based upon few genetic abnormalities/alteration. In fact, irregular
microvasculature and aberrant interstitium of solid tumors impose
significant pathophysiologic barrier functions against cancer treatment
modalities, hence novel strategies should holistically target
bioelements of tumor microenvironment (TME). In this study, we provide
some overview and insights on TME and important strategies used to
control the impacts of such pathophysiologic barriers.
Results: We reviewed all relevant
literature for the impacts of tumor interstitium and microvasculature
within the TME as well as the significance of the implemented
strategies. Results: While tumorigenesis initiation seems to be in close
relation with an emergence of hypoxia and alterations in
epigenetic/genetic materials, large panoplies of molecular events emerge
as intricate networks during oncogenesis to form unique lenient TME in
favor of tumor progression. Within such irregular interstitium, immune
system displays defective surveillance functionalities against malignant
cells. Solid tumors show multifacial traits with coadaptation and
self-regulation potentials, which bestow profound resistance against the
currently used conventional chemotherapy and immunotherapy agents that
target solely one face of the disease.
Conclusion: The cancerous cells
attain unique abilities to form its permissive microenvironment, wherein
(a) extracellular pH is dysregulated towards acidification, (b)
extracellular matrix (ECM) is deformed, (c) stromal cells are
cooperative with cancer cells, (d) immune system mechanisms are
defective, (e) non-integrated irregular microvasculature with pores
(120-1200 nm) are formed, and (h) interstitial fluid pressure is high.
All these phenomena are against cancer treatment modalities. As a
result, to control such abnormal pathophysiologic traits, novel cancer
therapy strategies need to be devised using multifunctional
nanomedicines and theranostics.