Targeting PIN1 enzyme for pancreatic cancer

Abstract

Hepatocellular carcinoma (HCC) is a major global health concern, ranking as the fourth most common cancer in men and eighth in women, with an alarming mortality rate. Despite advances in medical interventions, including surgical resection, liver transplantation, and molecular-targeted therapies like sorafenib and lenvatinib, outcomes for advanced HCC remain suboptimal. Protein phosphorylation and isomerization have emerged as critical regulators of cancer progression, with the peptidyl-prolyl cis-trans isomerase PIN1 playing a significant role in hepatocarcinogenesis. PIN1 is implicated in the stability and activity of key oncogenic and tumor suppressor proteins, driving uncontrolled cell proliferation and tumor growth in HCC. This review explores the molecular mechanisms by which PIN1 facilitates HCC progression, focusing on its interaction with cyclin D1 and its role in oncogenic signaling pathways. The research also highlights the potential of targeting PIN1 as a therapeutic strategy. Preclinical studies showed that PIN1 inhibition reduces tumor growth, induces cell death, and enhances survival in animal models. Moreover, PIN1 inhibitors like API-1, ATRA, and ATO have demonstrated promising anti-proliferative effects on HCC cells, paving the way for novel treatment avenues. Given the resistance challenges to current therapies like sorafenib, combining PIN1 inhibitors with existing drugs may offer enhanced efficacy and mitigate resistance. Further research is essential to understand PIN1-mediated pathways in drug resistance and to optimize PIN1-targeted therapies for clinical use. This review underscores the therapeutic potential of PIN1 inhibition in improving outcomes for HCC patients.