Development of target therapy for stromal cells

据报道，癌症相关成纤维细胞（CAFs）通过分泌细胞外基质蛋白、蛋白酶、细胞因子和生长因子来影响肿瘤进展。最近，CAFs的重要性被报道与对分子靶向治疗的耐药性有关。本研究表明，与体外对照CAFs相比，与表达PDPN的CAFs共培养时，携带EGFR激活突变的肺腺癌细胞系对EGFRTKI的抗性更强。此外，105例术后复发的PDPN阳性CAFs患者的EGFRTKIs反应明显低于PDPN阴性CAFs患者。我们的研究表明，PDPN阳性的CAFs在EGFRTKIs的原发性耐药中起重要作用，可能是与EGFRTKIs联合治疗的理想治疗靶点。

Cancer associated fibroblasts (CAFs) reportedly influence tumor progression via the secretion of extracellular matrix proteins, proteases, cytokines, and growth factors. Recently, the significance of CAFs was reported to be associated with resistance to molecular-targeted therapy.This study shows lung adenocarcinoma cell lines harboring EGFR activating mutation became more resistant to EGFRTKI when cocultured with PDPN expressing CAFs, compared with control CAFs in vitro. Furthermore, 105 postoperative recurrent patients with PDPN positive CAFs had a significantly lower EGFRTKIs response, compared with those with PDPN negative CAFs. Our studies show PDPN positive CAFs plays an important role in primary resistance to EGFRTKIs and may be an ideal therapeutic target for use in combination therapy with EGFRTKIs.