Degradation of FAK-targeting by proteolytic targeting chimera technology to inhibit the metastasis of hepatocellular carcinoma

Liver cancer is a prevalent malignant cancer,ranking third in terms of mortality rate.Metastasis and recurrence primarily contribute to the high mortality rate of liver cancer.Hepatocellular carcinoma(HCC)has low expression of focal adhesion kinase(FAK),which increases the risk of metastasis and recurrence.Nevertheless,the efficacy of FAK phosphorylation inhibitors is currently limited.Thus,investigating the mechanisms by which FAK affects HCC metastasis to develop targeted therapies for FAK may present a novel strategy to inhibit HCC metastasis.This study examined the correlation between FAK expression and the prognosis of HCC.Additionally,we explored the impact of FAK degradation on HCC metastasis through wound healing experiments,transwell invasion experiments,and a xenograft tumor model.The expression of proteins related to epithelial-mesenchymal transition(EMT)was measured to elucidate the underlying mechanisms.The results showed that FAK PROTAC can degrade FAK,inhibit the migration and invasion of HCC cells in vitro,and notably decrease the lung metastasis of HCC in vivo.Increased expression of E-cadherin and decreased expression of vimentin indicated that EMT was inhibited.Consequently,degradation of FAK through FAK PROTAC effectively suppressed liver cancer metastasis,holding significant clinical implications for treating liver cancer and developing innovative anti-neoplastic drugs.

Photocyanine:A novel and effective phthalocyanine-based photosensitizer for cancer treatment

As one of the three key components of photodynamic therapy(PDT),photosensitizers(PSs)greatly influence the photodynamic efficiency in the treatment of tumors.Photosensitizers with tetrapyrrole structure,such as porphyrins,chlorins and phthalocyanines,have been extensively investigated for PDT and some of them have already received clinical approval.However,only a few of porphyrin-based photosensitizers are available for clinical applications,and PDT has not received wide recognition in clinical practice.In this regard,PSs remain a limiting factor.Our research focuses on the rational design of new PSs.Photocyanine,a Zinc(Ⅱ)phthalo-cyanine(ZnPc)type photosensitizer with low dark toxicity and high single oxygen quantum yield,is one of the promising PSs candidates and currently being tested in clinical trials.Here,we present an overview on the development of Photocyanine,including its design,synthesis,purification,characterization and preclinical studies,wishing to contribute to the research of more promising PSs.