GSDM Researchers Published in Clinical & Experimental Metastasis

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The paper appeared in the May issue of Clinical & Experimental Metastasis.

Four Boston University Henry M. Goldman School of Dental Medicine (GSDM) researchers published a paper titled, “Bone microenvironment-mediated resistance of cancer cells to bisphosphonates and impact on bone osteocytes/stem cells,” in Clinical & Experimental Metastasis in May. The paper was authored by Abeer Alasmari DSc 17; Shish-Chun Lin MSc 15; Dr. Serge Dibart, Professor and Chair of the Department of Periodontology; and Dr. Erdjan Salih, Associate Professor in the Department of Periodontology.

In this paper, the researchers explored the interplay between cancer stem cells and osteocytes/osteoblasts and mesenchymal stem cells. Currently, bisphosphonates (BPs) are used clinically as anti-resorptive agents to treat a number of conditions including cancer-induced bone resorption. Many cancers with solid tumors, such as breast and prostate cancer, gravitate towards bone. This makes treatment much more challenging, and the question of why cancer cells take refuge in bone has not been definitely answered.

To learn more about the relationship between BPs and cancer cells, the researchers used a multidisciplinary approach which included expertise in medicinal/pharmaceutical chemistry, cell biology, biochemistry, pharmacology, cancer biology, bone biology, and state-of-the-art technologies. Their work investigated several areas of clinically used BPs for osteoporosis and cancer patients, as well as cancer-bone metastasis/interactions using the pioneered model systems developed in their laboratory.

The team’s results suggested that a direct anti-cancer effect of BPs in the bone microenvironment is not possible and that cancer-bone metastasis is independent of the bone remodeling stage.  These conclusions are contrary to widely held beliefs that cancer-bone metastasis is bone resorption dependent. The work revealed intricate details of cancer-bone metastasis and the impact of extensively used BPs on bone biology. Their research raised the possibility that the circulating cancer cells that are drawn to bone may not be a specific sub-population but instead may evolve after exposure to the bone microenvironment.

This research also sheds light on how and why clinically used bisphosphonates may generate untreatable clinical osteonecrosis of jaw bone observed in dental treatment centers, through the impact of mineral-bound bisphosphonates on osteocytes, which are embedded within the bone mineral. These findings and conceptual advances apply not only to prostate and breast cancers, but could be applicable to the clinical treatment of oral cancers as well.

“We are now ideally positioned to make a major impact in resolution of the chemotherapy resistance of cancers in the bone microenvironment and to develop new strategies and drugs with direct clinical translational potential using our unique model systems,” said Dr. Salih.