“When expressed, CA9 is the Achilles heel of a tumour; its presence plays a major role in the growth and metastasis of breast cancer. But, when we stop the production of CA9, or block its activity with drug inhibitors, the tumour doesn’t spread,” says Dr. Shoukat Dedhar, distinguished scientist, BC Cancer Agency, and primary investigator of the study.
“This enzyme is certainly involved in life-threatening cancer growth in some types of tumours. After examining 3,630 breast cancer tumours from patients followed over a long period of time, we found that CA9 was significantly linked to poor relapse and survival rates,” Dr. Dedhar explains.
The findings, published online in Cancer Research, show that in hypoxic (low oxygen) breast cancer tumours, CA9 protein levels are increased on the surfaces of the cancer cells. This gives rise to aggressive tumours that are prone to spread. The research delved further to find that when CA9 is eliminated by genetic targeting or by using novel drug inhibitors, the tumours regress.
Dr. Stephen Chia, chair, provincial breast tumour group, medical oncologist, BC Cancer Agency says, “These findings have potential life-saving qualities. If we can effectively target the root cause of metastasis in our patients with CA9 tumours, we will significantly reduce the deadly spread of disease.”
“Our research provides sufficient evidence to suggest that this enzyme is a relevant therapeutic target and inhibitor drug treatments should be used to treat CA9 positive breast, and other cancers in which CA9 expression is increased and linked to poor patient outcomes,” says Dr. Dedhar.
Dr. Dedhar’s group collaborated with Dr. Claudiu Supuran and his medicinal chemistry group in Florence, Italy, where they developed the two chemical classes of CA9 pharmacologic inhibitor compounds tested in this study. After proving that these inhibitor compounds not only successfully block the function of CA9, but also significantly block tumor growth and metastasis. Dr. Dedhar’s research team is now looking to ready the compounds for clinic-based testing.
“Clinical trials of these novel drugs that inhibit the CA9 enzyme need to be done to confirm the life saving benefits,” adds Dr. Karen Gelmon, medical oncologist, BC Cancer Agency, who facilitates clinical trials with breast cancer patients.
Preparing the compounds for clinic-based testing requires 18 to 24 months of extensive pharmacokinetic and toxicology testing before they could potentially be introduced in a phase 1 clinical trial.
“Dr. Dedhar’s collaborative approach with clinical colleagues within the BC Cancer Agency, and international Italian experts in pharmacology, is proof that together we can work effectively to unravel the cancer problem and find personalized solutions to treat our patient’s cancers effectively,” says Dr. Samuel Abraham, vice president, research, BC Cancer Agency.
The BC Cancer Agency, an agency of the Provincial Health Services Authority, is committed to reducing the incidence of cancer, reducing the mortality from cancer, and improving the quality of life of those living with cancer. It provides a comprehensive cancer control program for the people of British Columbia by working with community partners to deliver a range of oncology services, including prevention, early detection, diagnosis and treatment, research, education, supportive care, rehabilitation and palliative care. Visit www.bccancer.ca for more information. The BC Cancer Foundation, raises funds to support research and enhancements to patient care at the BC Cancer Agency.
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