Cyclophilin A: promising target in cancer therapy - Review

Sep 21, 2026

Upload by Quinn

Cyclophilin A (CypA), a prevalent immunophilin family member, functions not only as an intracellular receptor for cyclosporine A but also through its peptidyl-prolyl cis-trans isomerase (PPIase) activity, influencing protein folding, trafficking, immune modulation, and cell signaling. Evidence links CypA upregulation to multiple human cancers, suggesting its value as a therapeutic target. The review summarizes CypA’s multifaceted roles in cancer biology and examines strategies for therapeutic targeting of CypA to support novel cancer treatment development.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages13

Reading Time33 min

AccessFree to download

Introduction

Overview of cancer therapies and the need for new targets

Cyclophilins and CypA biology

Conserved cyclophilin family and PPIase activity

CypA as a CsA receptor and roles in disease

Therapeutic potential of targeting CypA in cancer

CANCER BIOLOGY & THERAPY 2024, VOL. 25, NO. 1, 2425127 [https://doi.org/10.1080/15384047.2024.2425127](https://doi.org/10.1080/15384047.2024.2425127) REVIEW Cyclophilin A: promising target in cancer therapy Shujuan Jin a, Mengjiao Zhangb, and Xiaoting Qiaoa aShenzhen Institute for Technology Innovation, National Institute of Metrology, Shenzhen, Guangdong, China; bChenxi Women’s and Children’s Hospital, Huaihua, Hunan, China ABSTRACT Cyclophilin A (CypA), a member of the immunophilin family, stands out as the most prevalent among the cyclophilins found in humans. Beyond serving as the intracellular receptor for the immunosuppressive drug cyclosporine A (CsA), CypA exerts critical functions within the cell via its peptidyl-prolyl cis-trans isomerase (PPIase) activity, which is crucial for processes, such as protein folding, trafficking, assembly, modulation of immune responses, and cell signaling. Increasing evidence indicates that CypA is upregulated in a variety of human cancers and it may be a novel potential therapeutic target for cancer treatment. Therefore, gaining a thorough understanding of CypA’s contribution to cancer could yield fresh perspectives and inform the development of innovative therapeutic approaches. This review delves into the multifaceted roles of CypA in cancer biology and explores the therapeutic potential of targeting CypA. ARTICLE HISTORY Received 15 April 2024 Revised 8 August 2024 Accepted 30 October 2024 KEYWORDS Cyclophilin a; PPIase; CD147; cell proliferation; cell invasion; drug resistance; Inhibitor; cancer therapy Introduction Various types of cancer pose a global threat to human life, and their complexity represents a significant challenge for the development of new therapeutic strategies. Currently, a range of cancer therapies have been developed, including surgery, chemotherapy, radiation therapy immunotherapy, and targeted therapy. 1–4 Among these, molecular targeted therapies are revolutionary therapeutics that interfere with specific molecules to inhibit cancer growth, progression, and metastasis. These therapies are useful either alone or in combination with standard chemotherapy agents. In fact, identifying an ideal target is essential for the successful development of molecular targeted therapies.5,6 Many studies have found several various biomarkers and signaling pathways that influence the malignant features of cancer cells, such as proliferation, anti-apoptosis, invasion, metastasis, angiogenesis, therapeutic resistance. Several molecular targeted therapies approved by the Food and Drug Administration (FDA) have demonstrated remarkable clinical success in treating various types of cancer, including breast, leukemia, colorectal, lung, and ovarian cancers.7–14 However, challenges like cancer metastasis, recurrence, heterogeneity, resistance to chemotherapy and radiation therapy can lead to treatment failure. 15 Therefore, early detection and identification of novel therapeutic targets are crucial for the development of more effective treatments. Cyclophilins are a conserved and ubiquitous family of proteins that are found in all living species, from Escherichia coli to Homo sapiens. 16 Generally, these proteins possess PPIases activity that catalyzes the trans to cis isomerization of peptide bonds on proline residues. 17 Indeed, owing to their enzymatic PPIase and/or binding activities, cyclophilins are involved in a wide variety of cellular processes, such as protein folding, trafficking, posttranslational modifications, protein assembly and cell signaling. 18 To date, at least 18 known human cyclophilins have been identified, including Cyclophilin A (CypA), Cyclophilin B (CypB), Cyclophilin C (CypC), Cyclophilin D (CypD) . 19 All members of the cyclophilin family share a common domain known as cyclophilin-like domain (CLD), which is surrounded by domains unique to each protein. The CLD of different cyclophilin contains from 145 to 180 amino acid resid

FAQs

What is Cyclophilin A (CypA) and what key activity does it have?

CypA is an immunophilin family member and acts through its peptidyl-prolyl cis-trans isomerase (PPIase) activity. It also serves as an intracellular receptor for cyclosporine A (CsA).

How does CypA relate to cancer progression?

The text states that CypA is overexpressed in several cancer types and promotes proliferation, anti-apoptosis, infiltration, and metastasis. This pattern supports CypA as a possible therapeutic target.

Why is molecular targeted therapy dependent on identifying an ideal target?

Molecular targeted therapies interfere with specific molecules to inhibit cancer growth and progression. The article emphasizes that identifying an ideal target is essential for successful development.

Sep 21, 2026

Upload by Quinn