Targeting prolyl isomerase Pin1 as a promising strategy to overcome resistance to cancer therapies

Abstract

The development of tumor therapeutic resistance is one of the important reasons for the failure of antitumor therapy. Starting with multiple targets and multiple signaling pathways is helpful in understanding the mechanism of tumor resistance. The overexpression of prolyl isomerase Pin1 is highly correlated with the malignancy of cancer, since Pin1 controls many oncogenes and tumor suppressors, as well as a variety of cancer-driving signaling pathways. Strikingly, numerous studies have shown that Pin1 is directly involved in therapeutic resistance. In this review, we mainly summarize the functions and mechanisms of Pin1 in therapeutic resistance of multifarious cancers, such as breast, liver, and pancreatic carcinomas. Furtherly, from the perspective of Pin1-driven cancer signaling pathways including Raf/MEK/ERK, PI3K/Akt, Wnt/β-catenin, NF-κB, as well as Pin1 inhibitors containing juglone, epigallocatechin-3-gallate (EGCG), all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), it is better to demonstrate the important potential role and mechanism of Pin1 in resistance and sensitization to cancer therapies. It will provide new therapeutic approaches for clinical reversal and prevention of tumor resistance by employing synergistic administration of Pin1 inhibitors and chemotherapeutics, implementing combination therapy of Pin1-related cancer signaling pathway inhibitors and Pin1 inhibitors, and exploiting novel Pin1-specific inhibitors.

Keywords: 5-Fluorouracil (PubChem CID: 3385); Adriamycin (PubChem CID: 31703); All-trans retinoic acid (PubChem CID: 444795); Arsenic trioxide (PubChem CID: 14888); Cancer-driving pathways; Cisplatin (PubChem CID: 5702198); Drug-resistant reversal and chemotherapy sensitization; Epigallocatechin-3-gallate (PubChem CID: 65064); Gefitinib (PubChem CID: 123631); Gemcitabine (PubChem CID: 60750); Juglone (PubChem CID: 3806); Paclitaxel (PubChem CID: 36314); Pin1 inhibitors; Prolyl isomerase Pin1; Sorafenib (PubChem CID: 216239); Tamoxifen (PubChem CID: 2733525); Tumor therapeutic resistance.