Therapeutic Targeting of Collagen Biosynthetic Enzymes in Cancer

This is the authors' abstract. We don't add key points for this paper.

The dynamic interplay between collagen and diverse cell types within the tumor microenvironment (TME) plays a critical role in tumor progression, drug resistance and metastasis. Dysregulated collagen biosynthesis, aberrant post-translational modifications of collagen, and excessive collagen deposition drive extracellular matrix (ECM) remodeling and promote tumor progression. Aberrant expression and activity of collagen-modifying enzymes, including prolyl-4-hydroxylases (P4Hs), procollagen-lysine, 2-oxoglutarate 5-dioxygenases (PLODs), and lysyl oxidase (LOX) across cancer subtypes contribute to tumor stiffness, angiogenesis, invasion, metastasis, and therapeutic resistance. Additionally, emerging evidence suggests that collagen-modifying enzymes represent attractive targets for cancer therapy. Therefore, this review examines the molecular mechanisms underlying the roles of these enzymes in cancer progression, with particular emphasis on matrix cross-linking, hypoxic adaptation, and metastatic dissemination. It also highlights recent advances in the development of inhibitors targeting collagen-modifying enzymes, along with their therapeutic potential, challenges in clinical translation, and opportunities for combination strategies. Targeting the collagen-modifying enzymes offers promising avenues for disrupting the TME and improving cancer treatment outcomes. Furthermore, understanding the interplay between collagen-modifying enzymes and cancer progression will open novel avenues for developing targeted therapies aimed at disrupting the TME and improving patient outcomes.