Publication: Targeting Lysyl Oxidase Family Meditated Matrix Cross-Linking as an Anti-Stromal Therapy in Solid Tumours

Thomas R. Cox, Jan 2021

Targeting Lysyl Oxidase Family Meditated Matrix Cross-Linking as an Anti-Stromal Therapy in Solid Tumours

Congratulations to Kaitlin and Yordanos who just had their co-first author review published in Cancers as part of a special edition on Treating the Cancer Matrix: Progress in the Identification of Potential Therapeutic Targets. Also a shout out to Rhiannon for her amazing illustrator skills and creating some beautiful figures. And finally to Jess, who as co-senior author played an instrumental role in bringing everything together.

Extracellular matrix in cancer
Remodeling of the extracellular matrix (ECM) in solid tumours. In healthy tissue, the ECM has a structured basement membrane consisting primarily of collagens IV and VI as well as a scaffolding arrangement of fibrillar collagens that are predominantly secreted by the fibroblasts. In comparison, solid tumours typically consist of more densely packed, aberrantly cross-linked fibrillar collagens resulting from the recruitment and activation of CAFs. As the level of deposition of fibrillar collagens such as collagens I, III and V increases in the tumour ECM, so too does LOX family mediated collagen cross-linking. In addition, tumour ECM results in a breakdown of the structure of the normal basement membrane.

Abstract

The lysyl oxidase (LOX) family of enzymes are a major driver in the biogenesis of desmoplastic matrix at the primary tumour and secondary metastatic sites. With the increasing interest in and development of anti-stromal therapies aimed at improving clinical outcomes of cancer patients, the Lox family has emerged as a potentially powerful clinical target. This review examines how lysyl oxidase family dysregulation in solid cancers contributes to disease progression and poor patient outcomes, as well as an evaluation of the preclinical landscape of LOX family targeting therapeutics. We also discuss the suitability of the LOX family as a diagnostic and/or prognostic marker in solid tumours.

Links

View the Open-Access article on the Cancers website here

Citation

Setargew YFI*, Wyllie K*, Grant RD, Chitty JL and Cox TR
Cancers (2021) | doi: 10.3390/cancers13030491

Funding

T.R.C., J.L.C., R.D.G., Y.F.I.S. and K.W. are supported by the National Health and Medical Research Council (NHMRC), Cancer Institute NSW, Cancer Council NSW, Perpetual IMPACT, Love Your Sister in association with the Australian National Breast Cancer Foundation, and Susan G Komen for the Cure. TRC is a recipient of a NHMRC RD Wright Biomedical Career Development Fellowship.