PF-573228

Genetic knockout of FAK or pharmacological inhibition using defactinib or PF-573228 effectively suppressed the sorafenib-induced upregulation of AKT and HMGCR...Importantly, another RAF-targeting multikinase inhibitor, regorafenib, also triggered a similar adaptive FAK-cholesterol response, suggesting that this may be a common resistance mechanism shared among RAF inhibitors...Collectively, this study systematically uncovers a new mechanism of sorafenib resistance in HCC: downregulation of RhoE drives cholesterol biosynthesis through activation of the FAK/AKT axis, thereby activating the SHH pathway and upregulating GLI1. These findings provide a strong theoretical rationale for the use of FAK inhibitors to overcome resistance and highlight the dual clinical relevance of the cholesterol biosynthesis gene signature-both as a molecular marker for predicting resistance and as a potential guide for personalized treatment strategies in HCC.

To our knowledge, this is the first report demonstrating the role of FAK and its inhibition across both normal and cancerous bladder urothelial models. This study highlights the critical role of FAK in the progression of human bladder cancer and establishes a foundation for exploring FAK inhibition as a potential therapeutic approach in bladder cancer treatment.

Furthermore, deactivation of FAK using siFAK or FAK inhibitor (PF-573228, PF) synergistically contributed to PTK7 knockdown-inhibited FAK activity, MMP7 expression, and the migration and invasion abilities of HCC cells. Collectively, our findings show that PTK7 mediates HCC progression by regulating the MTA2-FAK-MMP7 axis and may be a diagnostic value for HCC patients.

The results indicated that SYT13 promoted the malignant phenotypes of breast cancer cells by the activation of FAK/AKT signaling pathway.

The inhibition of FAK activation by PF573228 significantly attenuated the oncogenic effect of TPT1-AS1. These findings indicated that TPT1-AS1 promoted tumour progression and metastasis in CRC by upregulating TPT1 levels and activating the FAK and JAK-STAT3 signalling pathways. Thus, TPT1-AS1 may be considered as a potential therapeutic target for CRC.

Our results indicate that FAK inhibition arrests GBM cell proliferation, resulting in cell senescence, and pinpoint p62 as being key to this process. These findings highlight the possible therapeutic value of targeting FAK in GBM.