title: Lysyl Oxidase, a Targetable Secreted Molecule Involved in Cancer Metastasis.
abstract: Secondary metastatic cancer remains the single biggest cause of mortality and morbidity across most solid tumors. In breast cancer, 100% of deaths are attributed to metastasis. At present, there are no "cures" for secondary metastatic cancer of any form and there is an urgent unmet clinical need to improve the tools available in our arsenal against this disease, both in terms of treatment, but also prevention. Recently, we showed that hypoxic induction of the extracellular matrix modifying enzyme lysyl oxidase (LOX) correlates with metastatic dissemination to the bone in estrogen receptor negative breast cancer and is essential for the formation of premetastatic osteolytic lesions. We showed that in models of breast cancer metastasis, targeting LOX, or its downstream effects, significantly inhibited premetastatic niche formation and the resulting metastatic burden, offering preclinical validation of this enzyme as a therapeutic target for metastatic breast cancer. Our work is the latest in an emerging body of work supporting the targeting of LOX and calls for greater efforts in developing therapeutics against this extracellular secreted factor in the prevention of cancer progression across multiple solid tumor types.
authors.affiliation: Biotech Research and Innovation Centre (BRIC), University of Copenhagen (UCPH), Copenhagen, Denmark. thomas.cox@bric.ku.dk.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Cox
authors.affiliation: The Mellanby Centre for Bone Research, The University of Sheffield, Sheffield, United Kingdom.
authors.forename: Alison
authors.initials: A
authors.lastname: Gartland
authors.affiliation: Biotech Research and Innovation Centre (BRIC), University of Copenhagen (UCPH), Copenhagen, Denmark.
authors.forename: Janine T
authors.initials: JT
authors.lastname: Erler
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism*; D015687:Cell Hypoxia / Q000235:genetics*; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009362:Neoplasm Metastasis; D008249:Protein-Lysine 6-Oxidase / Q000235:genetics*
chemical_list: D008249:Protein-Lysine 6-Oxidase