Title:Targeting Tumor Microenvironment with Silibinin: Promise and Potential for a Translational Cancer Chemopreventive Strategy
Volume: 13
Issue: 5
Author(s): Gagan Deep and Rajesh Agarwal
Affiliation:
Keywords:
Angiogenesis, Chemoprevention, Inflammation, Metastasis, Silibinin, Tumor microenvironment.
Abstract: Tumor microenvironment (TME) refers to the dynamic cellular and extra-cellular components surrounding
tumor cells at each stage of the carcinogenesis. TME has now emerged as an integral and inseparable part of the
carcinogenesis that plays a critical role in tumor growth, angiogenesis, epithelial to mesenchymal transition (EMT),
invasion, migration and metastasis. Besides its vital role in carcinogenesis, TME is also a better drug target because of its
relative genetic stability with lesser probability for the development of drug-resistance. Several drugs targeting the TME
(endothelial cells, macrophages, cancer-associated fibroblasts, or extra-cellular matrix) have either been approved or are
in clinical trials. Recently, non-steroidal anti-inflammatory drugs targeting inflammation were reported to also prevent
several cancers. These exciting developments suggest that cancer chemopreventive strategies targeting both tumor and
TME would be better and effective towards preventing, retarding or reversing the process of carcinogenesis. Here, we
have reviewed the effect of a well established hepatoprotective and chemopreventive agent silibinin on cellular
(endothelial, fibroblast and immune cells) and non-cellular components (cytokines, growth factors, proteinases etc.) of the
TME. Silibinin targets TME constituents as well as their interaction with cancer cells, thereby inhibiting tumor growth,
angiogenesis, inflammation, EMT, and metastasis. Silibinin is already in clinical trials, and based upon completed studies
we suggest that its chemopreventive effectiveness should be verified through its effect on biological end points in both
tumor and TME. Overall, we believe that the chemopreventive strategies targeting both tumor and TME have practical
and translational utility in lowering the cancer burden.
