Fig. 7: Schematic diagram represents the regulatory role of tumor cell-rCAF crosstalk in chemoresistance. | npj Precision Oncology

Fig. 7: Schematic diagram represents the regulatory role of tumor cell-rCAF crosstalk in chemoresistance.

From: Chemoresistant fibroblasts dictate neoadjuvant chemotherapeutic response of head and neck cancer via TGFα-EGFR paracrine signaling

Fig. 7

In chemoresistant HNSCC patients, the population of CAFs in tumors remains unchanged before and after receiving NACT treatment. Mechanistically, the elevated PI3K/AKT/p65 signaling pathway in rCAFs prohibits chemotherapy-induced cell death and up-regulates TGFα secretion. rCAF-secreted TGFα then binds and activates its receptor EGFR in cancer cells, which subsequently up-regulates its downstream Src/STAT3 mediated survival pathway and represses p53/caspase-3 dependent apoptosis to cause tumor chemoresistance. Clinically, the elevated TGFα serum level determines NACT response in patients with HNSCC, while treatment with clinically approved anti-EGFR cetuximab can rescue chemotherapeutic response in tumors that are derived from co-injection of cancer cells and rCAFs in vivo.

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