State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China.
Department of Pharmacology and Therapeutics, Faculty of Pharmacy (FOP), University of Central Punjab, Lahore, Pakistan.
Curr Drug Targets. 2018;19(13):1573-1588. doi: 10.2174/1389450119666180219124439.
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.
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.
肿瘤的生长、发展、进展、转移、侵袭和耐药性仅取决于周围细胞、细胞外基质和肿瘤微环境（TME）的募集。TME 直接和间接地与癌相关成纤维细胞（CAF）有关。CAF 与肿瘤周围细胞的相互作用、它们的起源、激活、转化以及招募其他非肿瘤细胞来缓解肿瘤的能力非常复杂，长期以来一直是研究的热点。本研究深入探讨了 CAF，并强调了其作为 TME 调节剂的潜在靶点，同时讨论了目前针对 CAF 的临床试验中的药物。
CAF 在抗肿瘤治疗中的潜在作用基于其对药物的一致反应，通过这些遗传上更稳定且具有抗免疫支持作用的 CAF 细胞针对不同的肿瘤部位。CAF 可以通过免疫系统、生长因子（GF）包括转化生长因子（TGF）、血管内皮 GF、成纤维细胞 GF、血小板衍生 GF 以及 TME 元素包括缺氧、碳酸酐酶、细胞外基质（ECM）来靶向。这些 CAF 的特征使其最容易受到单一和联合抗肿瘤治疗的影响，以产生协同或相加的效果。需要进一步研究 CAF 的潜在活性、起源机制和精细生物标志物的鉴定。这些激动人心的事实相互交织，预示着通过 CAF 在各个层面（包括临床前和临床试验）进行的新型治疗方法的研究取得进展，并具有进一步探索的巨大潜力。
