Nature Communications journal published two (1, 2) concurrent studies from McGill University researchers detailing the effectiveness of a current drug against two different types of cancer. Both forms are caused by mutations in the same gene, SMARCA4.
Initial work was focused on small cell carcinoma of the ovary, hypercalcemic type (SCCOHT), an uncommon but highly aggressive type of cancer which frequently affects younger women and is associated with a poor prognosis. The team found that targeting the cyclin-dependent kinases 4/6 (CDK4/6) exposed a vulnerability in SMARCA4-deficient cancers. This was done using FDA approved blockers for treating ER positive, HER2 negative advanced breast 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”, explained Dr. William Foulkes, Professor in the Departments of Medicine, Oncology and Human Genetics.
While much more common than SCCOHT, non-small cell lung cancer (NSCLC) can similarly be difficult to treat. The American Cancer Society estimates approximately 220,000 new diagnoses of NSCLC each year, compared to the 300 recorded cases of SCCOHT. In their investigations, researchers found that about 10% of NSCLC were also lacking SMARCA4.
“The fact these drugs worked so well was a bit surprising”, says Dr. Foulkes. “Perhaps it works because the protein which is targeted is at critically low levels in the tumour – just enough to keep the tumour alive, but still susceptible to blocking”.
With both in vitro and in vivo testing showing positive results, the next step would be human clinical trials.
“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”, added Dr. Sidong Huang, Assistant Professor in the Department of Biochemistry at McGill’s Faculty of Medicine, and senior author on both papers. “Furthermore, patients may also benefit from the anti-tumour immunity triggered by CDK4/6 inhibitors as recently shown in other cancers, in addition to the direct tumour inhibition by these drugs”.
HOPE RISES With Us!