Breast cancer at bone metastatic sites: recent discoveries and treatment targets |
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Authors: | Osama Hussein Svetlana V Komarova |
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Institution: | (1) Faculty of Dentistry, McGill University, Montreal, Quebec, H3A 1A4, Canada;(2) 740 Dr. Penfield Ave, 2201, Montreal, Quebec, Canada, H3A 1A4;(3) Present address: Faculty of Medicine, Mansoura University, Mansoura, 35516, Egypt; |
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Abstract: | Breast carcinoma is the most common cancer of women. Bones are often involved with breast carcinoma metastases with the resulting
morbidity and reduced quality of life. Breast cancer cells arriving at bone tissues mount supportive microenvironment by recruiting
and modulating the activity of several host tissue cell types including the specialized bone cells osteoblasts and osteoclasts.
Pathologically activated osteoclasts produce osteolytic lesions associated with bone pain, pathological fractures, cord compression
and other complications of metastatic breast carcinoma at bone. Over the last decade there has been enormous growth of knowledge
in the field of osteoclasts biology both in the physiological state and in the tumor microenvironment. This knowledge allowed
the development and implementation of several targeted therapeutics that expanded the armamentarium of the oncologists dealing
with the metastases-associated osteolytic disease. While the interactions of cancer cells with resident bone cells at the
established metastatic gross lesions are well-studied, the preclinical events that underlie the progression of disseminated
tumor cells into micrometastases and then into clinically-overt macrometastases are just starting to be uncovered. In this
review, we discuss the established information and the most recent discoveries in the pathogenesis of osteolytic metastases
of breast cancer, as well as the corresponding investigational drugs that have been introduced into clinical development. |
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Keywords: | Bone metastases Breast cancer Osteoclast Osteoblast Metastatic niche Drug development |
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