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null Study identifies strategies to reduce breast cancer growth and related skeletal lesions

RI-MUHC team publishes findings in the journal, Bone Research

July 23, 2020

Source: RI-MUHC. Bone metastasis is a major cause of morbidity and mortality in patients with breast cancer. However, current therapeutic approaches against breast cancer induced bone metastasis are mostly palliative and have minimal effect on cancer progression.

In a recent paper published in Bone Research, a team of researchers led by Shafaat Rabbani, MD, at the Research Institute of the McGill University Health Centre (RI-MUHC) has presented a novel approach to target both tumour growth and the skeletal lesions caused by breast cancer-induced bone disease.

Summary of the anticancer effect of huATN-658 + Zometa combination.
Summary of the anticancer effect of huATN-658 + Zometa combination.

“There is an unmet need for the development and validation of an effective therapeutic strategy that could block breast tumour growth once it has spread to the secondary organs like bone,” explains Dr. Rabbani, who is a senior scientist in the Metabolic Disorders and Complications (MeDiC) Program at the RI-MUHC.

Previous studies conducted by the Rabbani lab have shown that a protein called urokinase plasminogen activator receptor (uPAR) plays a major role in tumour growth and metastasis in hormone dependent malignancies like breast and prostate cancer. Higher levels of uPAR expression show a direct correlation with tumour aggressiveness in patients with several common cancers including breast cancer, which led to the identification of uPAR as an attractive diagnostic, prognostic, and therapeutic target in cancer.

Doctoral student Niaz Mahmood and lab supervisor Ani Arakelian, worked in collaboration with Dr. Andrew P. Mazar of Monopar Therapeutics in Illinois and Drs. Haseeb Ahmed Khan and Imrana Tanvir of the Fatima Memorial Hospital System in Lahore, Pakistan. They examined the anti-tumour effects of an anti-uPAR antibody to assess the effect on skeletal lesions in vitro and in vivo studies.

Doctoral student Niaz Mahmood (right) and Lab supervisor Ani Arakelian (left) with RI-MUHC senior scientist Dr. Shafaat Rabbani. (Fall 2019)
Doctoral student Niaz Mahmood (right) and Lab supervisor Ani Arakelian (left) with RI-MUHC senior scientist Dr. Shafaat Rabbani. (Fall 2019)

Results from the study showed that the antibody reduced tumour growth and reduced skeletal lesions, both independently and in combination therapy.

“Our goal is effective anticancer therapeutic strategies that can reduce breast tumour growth in nonskeletal and skeletal sites”, says Niaz Mahmood, lead author on the study. “We are one step closer now.”

About the study

Mahmood, N., Arakelian, A., Khan, H.A., Tanvir, I., Mazar, A.P., and Rabbani, S.A. uPAR antibody (huATN-658) and Zometa reduce breast cancer growth and skeletal lesions. Bone Res 8, 18 (2020). https://doi.org/10.1038/s41413-020-0094-3

The study was supported by a grant from the Canadian Institutes of Health Research.