Abstract
Background and Objective: Tumor growth, development, progression, metastasis, invasion and resistivity against drugs solely depend on the recruitment of surrounding cells, extracellular matrix and Tumor Microenvironment (TME). TME is directly as well as indirectly associated with Cancer- Associated Fibroblasts (CAF). The interactions of CAF with tumor surrounding cells, their origination, activation, transformation and ability to recruit other non-tumor cells for the clemency of tumor, are very complex and under active research since long. This study provides an in-depth review of CAF and highlights its potential targets for the regulation of TME as well as discusses current drugs in clinical trials, targeting through CAF.
Conclusion: The potential role of CAF in anti-tumor therapy is based on its coherent response against drugs, targeting different tumor sections through these genetically more stable and anti-immunosupportive CAF cells. CAF can be targeted through immunity system; Growth Factors (GF) including Transforming growth factor (TGF), vascular endothelial GF, fibroblast GF, platelet derived GF; and TME elements including hypoxia, carbonic anhydrase, extracellular matrix (ECM). Collectively these features of CAF make it most vulnerable against single as well as combinational, anti-tumor therapy for synergistic or additive effects. Potential activities of CAF, their origination mechanisms and identification of meticulous bio-markers are needed to be investigated further. The rousing facts about them mutually culminate the anticipation of progress towards novel therapeutic establishment against cancer through CAFs that are under progressive research at all levels including, pre-clinical and clinical trials as well as possess much potential to be explored further.
Keywords: Tumor microenvironment, hypoxia, synergetic effect, genetic stability, biomarkers, drug resistance, anti immunosupportive.
Graphical Abstract
61
11