Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT), is a particularly devastating cancer commonly diagnosed in women in their twenties and often has a very poor prognosis. In a recent study, researchers with the BC Cancer Research Institute have uncovered a metabolic vulnerability present in SCCOHT cells which may be a target for future treatment options.
“Finding this vulnerability and identifying a way to exploit it could have a huge impact for anyone diagnosed with this rare disease,” said Jennifer Ji, a BC Cancer Research Institute trainee and an MD/PhD candidate at the University of British Columbia who authored the study.
Jennifer and a team of BC Cancer researchers led by Dr. David Huntsman, a distinguished scientist at BC Cancer Research Institute and Canada Research Chair in Molecular and Genomic Pathology, found that SCCOHT cancer cells have very low levels of a metabolic enzyme called argininosuccinate synthase (ASS1), which is necessary for the production of arginine, an amino acid responsible for important cell functions including building proteins.
They discovered that while non-cancerous cells have higher levels of ASS1 and can produce their own arginine, SCCOHT tumours cannot produce their own. This means that they must be in an arginine-rich environment to survive. Using a small molecule called ADI-PEG20, the team has found a way to eliminate arginine in the tumour environment, essentially starving the cancer to death while having minimal effect on normal cells.
“This agent basically absorbs all of the arginine within the tumour environment so cells can’t produce it themselves,” explained Dr. David Huntsman. “It’s also possible that other cancers could have similar vulnerabilities and we are looking to partner with other research organizations who are evaluating these treatment options in patients whose cancer lacks the expression of this particular enzyme.”
The discovery is welcome news to Justin Mattioli, whose 34-year-old wife Eileen, succumbed to SCCOHT in May 2019. Prior to her passing, Eileen made the decision to donate her tissue samples to help advance cancer research in the hopes of finding new treatments for others facing the disease.
"We would hate to see someone else go through what Eileen did," says Justin. "And there is a good possibility that this may help advance further research into other types of cancers as well."
Eileen’s donated samples are now being used as a new cell model being developed by BC Cancer staff scientist Dr. Yemin Wang who has been leading studies into this rare cancer type. These cells will enable researchers to test the effects of new treatments on a cellular level and help to better understand the biology of SCCOHT. “Thanks to Eileen’s generous donation, we have access to one of only a handful of SCCOHT cell models available in the world to study this disease. This development will go a long way to better advancing our understanding of SCCOHT.”
The study was funded by the Terry Fox Research Institute, the BC Cancer Foundation, National Institutes of Health, Canadian Cancer Society, VGH & UBC Hospital Foundation and a number of other funding partners.