Drug Treating Breast Cancer May Be Effective in Treating Lung and Ovarian Cancer

SCCOHT

Two new papers, published simultaneously in Nature Communications and led by researchers at McGill University, offer promise that a drug currently used to treat estrogen positive breast cancer may be effective in treating two different types of cancer, one rare and one common form.

The breakthrough discovery launching this research came in 2014 when Dr. William Foulkes, James McGill Professor in the Departments of Medicine, Oncology and Human Genetics at McGill’s Faculty of Medicine, showed that small cell carcinoma of the ovary, hypercalcemic type (SCCOHT), a rare but highly fatal cancer which primarily strikes younger women, is caused by mutations in the gene SMARCA4.

The challenge became how to find a way to exploit this genetic deficiency to better treat these patients. Stepping up to the challenge was Dr. Sidong Huang, Assistant Professor in the Department of Biochemistry at McGill’s Faculty of Medicine, and senior author on both papers. Having trained for many years in Functional Genomics, Dr. Huang joined McGill with the goal of working on important problems in oncology. “Working on something like SCCOHT seemed an obvious choice as it is a unique genetic disease driven by loss of a single gene, SMARCA4,” explains Dr. Huang, who is also a member of McGill’s Goodman Cancer Research Centre.

A collaboration between Dr. Huang and Dr. Foulkes ensued, along with fellow McGill Professor Dr. Janusz Rak at the Research Institute of the McGill University Health Centre (RI-MUHC), Dr. Barbara Vanderhyden at the Ottawa Hospital Research Institute and Dr. Sriram Venneti at the University of Michigan. Through their work, Dr. Huang and his PhD student Yibo Xue, the papers’ first author, were able to identify that targeting the cyclin-dependent kinases 4/6 (CDK4/6) exposed a vulnerability in SMARCA4-deficient cancers.

“What’s clinically exciting about this work is that CDK4/6 inhibitors have been used for years, so they are very well known and their safety profile is established,” notes Dr. Foulkes who is also Head of the Cancer Genetics Laboratory at the Lady Davis Institute of the Jewish General Hospital and a researcher at the RI-MUHC.

“In the case of SCCOHT, in particular, it is encouraging to find existing drugs that may prove effective because this is such a rare cancer that it is unlikely to be the subject of dedicated drug development,” adds Dr. Huang. “Furthermore, patients may also benefit from the anti-tumor immunity triggered by CDK4/6 inhibitors as recently shown in other cancers, in addition to the direct tumor inhibition by these drugs”.

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