TY - JOUR

T1 - Lysyl Oxidase, a Targetable Secreted Molecule Involved in Cancer Metastasis

AU - Cox, Thomas Robert

AU - Gartland, Alison

AU - Erler, Janine T

N1 - ©2016 American Association for Cancer Research.

PY - 2016/1/15

Y1 - 2016/1/15

N2 - 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.

AB - 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.

KW - Breast Neoplasms

KW - Cell Hypoxia

KW - Cell Line, Tumor

KW - Female

KW - Gene Expression Regulation, Neoplastic

KW - Humans

KW - Neoplasm Metastasis

KW - Protein-Lysine 6-Oxidase

KW - Journal Article

KW - Review

U2 - 10.1158/0008-5472.CAN-15-2306

DO - 10.1158/0008-5472.CAN-15-2306

M3 - Review

C2 - 26732355

VL - 76

SP - 188

EP - 192

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 2

ER -