When herbs meets cancer; how to undersrtand and surmout the limitid achievement of high-grade tumor chemotherapy by natural occurring compunds

Abstract

Multidisciplinary approach and intertwining between technology, medicinal chemistry and molecular biology is a markof a new era of biomedicine and pharmacology. Built on this platform,vigorous success of highlyspecific onco-therapiestowardcertain malignant phenotype as well as tumor microenvironment constituents from stromal to endothelial and immune infiltrating cells, was expected. Inadequateachievement and unclear correlation between individual response to applied treatment and expression of relevant molecules in tumor tissue, remind us that despite all biotechnological improvements, understanding of this pathologyis still vastly limited. This especially refers to high grade tumors, with anaplastic cell fraction, aggressive features of tumor microenvironment and high metastatic potential. Even the criterium for low overall toxicity of molecular therapies was not contented, since the applied therapeutics, apart from their specific targets, share certain homology with molecules involved in cell physiology maintenance and normal biological function of healthy cells, making them unwanted off targets for specific drugs. In tumor types not indicated for targeted therapy, as well as those withinitially or acquiredresistance to treatment, chemotherapy of choice is usually based on combination of different drugs with nonselective toxicity against highly proliferative transformed cells. Limited success of radio/chemotherapy in advanced cancers is tightly connected with rapid tumor repopulation as a boomerang effect of aggressive treatments.This effectbrought on the surface the sophisticated communication between cells in tumor microenvironment, discovering prompt cell division in response to death induction. To avoid mitogenic signals delivered from injuredtumor tissue to neighboring anaplastic cells, reprogram of low/undifferentiatedcell fraction is required. At the level of the tissue, this means conversion of high-grade into low- grade, less aggressive tumor with promising response to established therapeutic protocols. Naturally occurring compounds presented a rich source of molecules with confirmedtumoricidal and immunomodulatorypotential. Despite numerous ethnobotanical and scientific data, their use in official medicine is still viewed with distrust. This is partly justified because of their high input on cell physiology at multiple levels affecting the outcome of the treatment. However, their potential to trigger the change of the malignant phenotype into more quiescent, functionally devoted form,near to the healthy counterpart of the same or different tissue is mainly unexplored, opening many opportunities in fundamental and applicable level. Differentiation inducing properties of natural products and their incorporation into actual protocols will be discussed.