Role of Collagen Regulators in Cancer Treatment: A Comprehensive Review

Abstract

Collagen is the most important structural protein and also the main component of the extra-cellular matrix (ECM). It plays a role in tumor progression. Collagen can be regulated by altering its biosynthesis pathway through various signaling pathways, receptors, and genes. The activity of cancer cells can also be regulated by other ECM components like metalloproteinases, hyaluronic acid, fibronectin, and so on. Hypoxia is also one of the conditions that lead to cancer progression by stimulating the expression of procollagen lysine as a collagen crosslinker, which increases the size of collagen fibres promoting cancer spread. The collagen content in cancerous cells leads to resistance to chemotherapy. So, to reduce this resistance, some collagen-regulating therapies are introduced, including inhibiting its biosynthesis, disturbing cancer cell signaling pathway, mediating ECM components, and directly utilizing collagenase. This study is an effort to compile the strategies reported to control the collagen level and different collagen inhibitors reported so far. More research is needed in this area. Growing understanding of collagen's structural features and its role in cancer progression will aid in the advancement of newer chemotherapies.

Keywords: Collagen; ECM; collagen remodeling; signalling pathways; therapy resistance; tumour microenvironment.