Targeting collagen Prolyl 4-hydroxylase for cancer treatment

Collagen prolyl 4-hydroxylase (C-P4H) is a critical enzyme involved in collagen biosynthesis, mediating the hydroxylation of proline residues to ensure the stability of collagen and its integration into the extracellular matrix (ECM). Within the tumor microenvironment (TME), aberrant ECM remodeling, characterized by excessive collagen deposition, contributes to tumor progression, metastasis, and resistance to therapy. C-P4H operates as an α2β2 tetramer, comprising three isoenzymes distinguished by their catalytic α-subunits (P4HA1, P4HA2, P4HA3) and a common β-subunit (P4HB). Both P4HAs and P4HB are frequently overexpressed in various cancers, where they facilitate ECM remodeling, cancer cell invasion, and metastasis. Inhibitors targeting P4HAs or P4HB have demonstrated promising anti-tumor effects, highlighting its potential as a therapeutic target. This review consolidates recent advancements in the comprehension of the roles and regulatory mechanisms of C-P4H in cancer progression and evaluates the development of C-P4H targeted therapies for prospective cancer treatment.