​A new study by researchers with the BC Cancer Research Institute and McGill University has revealed that the popular dietary supplement Alanine may offer an effective treatment option for people diagnosed with several types of aggressive cancer.  

The findings, published in Nature Communications, show alanine's potential as a treatment for cancers characterized by a dual loss of the SMARCA4 and SMARCA2 genes. These SMARCA4/2-deficient cancers include small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) — a rare and lethal tumour that occurs predominantly in women in their mid-twenties — as well as other malignancies, including a subset of lung cancers.

Currently, there are few effective treatments for these forms of cancer, which are often highly resistant to conventional chemotherapies and have very poor outcomes.

"Through an unbiased genome-wide screen, our teams identified the key metabolic change that enables the development of the aggressive SMARCA4/2-deficient cancers," said Dr. Yemin Wang, staff scientist in the Molecular Oncology department at the BC Cancer Research Institute, adjunct professor in UBC's department of laboratory medicine and co-lead author of the study. "This finding not only helps us better understand the biology of these cancers, but also provided multiple potential treatment strategies, alone or in combination with chemotherapy or immunotherapy, for clinical validation."

Alanine is an amino acid commonly found in meat and poultry, fish, eggs and dairy products, as well as some protein-rich plant foods. It is also available in powder form as a dietary supplement sold by health food retailers. It has been known to boost the body's immune system and is popular within the body-building community.

The study shows that alanine can kill SMARCA4/2-deficient cancers cells by interrupting the metabolic pathways they depend on.

The findings build on work by study co-author Dr. David Huntsman, distinguished scientist and co-founder of OVCARE, BC Cancer's multidisciplinary gynecologic cancer research team and professor in the departments of pathology and laboratory medicine and obstetrics and gynaecology at UBC. Dr. Huntsman and his team previously discovered the key role that the SMARCA4 and SMARCA2 genes play in cancers like SCCOHT.  

"This is a tremendous example of how studying a distinctive rare cancer, in this case small cell hypercalcemic ovarian cancers, can lead to insights that could impact other more common cancers," said Dr. Huntsman. "Most chemotherapies target all dividing cells, not just cancer cells, which is why side effects can be so difficult for patients. We were surprised and are excited by how specific this metabolic vulnerability is and its promise for a treatment approach that could be both more effective and less toxic."

The study was a multi-year collaboration led by researchers at BC Cancer, UBC and McGill University. Having established alanine's efficacy in the lab, the researchers now hope to take the findings into clinical trials.

"The next important stage is to have proper clinical testing to be conclusive, to say whether or not this is actually effective," said Dr. Sidong Huang, an associate professor at McGill University and the Rosalind and Morris Goodman Cancer Institute, and co-lead author of the report. "Even though it is very safe for most people, if you have an underlying condition such as a metabolism disease, it might not be safe to take this. We just want to be sure patients can tolerate high-dose alanine. It's important to talk to your doctor."

The study was funded by the Canadian Institutes of Health Research, Terry Fox Research Institute, Canadian Cancer Society, the BC Cancer Foundation, the VGH & UBC Hospital Foundation and a number of other funding partners.

^{This story is adapted from an article published by the UBC Faculty of Medicine and originally published by McGill University.}