Medications currently approved to treat some kinds of breast cancer — generally called CDK4/6 inhibitors — could be re-purposed to treat a rare type of ovarian cancer called small cell carcinoma of the ovary, hypercalcemic type (SCCOHT), a study suggests.
The study, “CDK4/6 inhibitors target SMARCA4-determined cyclin D1 deficiency in hypercalcemic small cell carcinoma of the ovary,” was published in Nature Communications.
The researchers had previously discovered that cells in SCCOHT, a rare and often fatal type of ovarian cancer, have mutations in the SMARCA4 gene.
“Working on something like SCCOHT seemed an obvious choice as it is a unique genetic disease driven by loss of a single gene, SMARCA4,” Sidong Huang, one of the researchers, said in a press release.
On its own, this information isn’t that clinically useful — it’s much easier to stop cancer by inactivating a change that’s driving the disease than by trying to somehow add back a fixed version of a mutated gene.
However, the study revealed that cancer cells with mutations in SMARCA4 might be vulnerable to targeting CDK4/6 — a protein complex that is important for cells, including cancer cells, to divide and grow.
The investigators discovered this by screening SCCOHT cell lines with RNA-based inhibitors of a wide variety of genes. They found that, when CDK4/6 was inhibited, the cells weren’t able to grow.
“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,” said William Foulkes, another researcher in the study.
The CDK4/6 inhibitors Kisqali (ribociclib) by Novartis, Ibrance (palbocliclib) by Pfizer, and Verzenio (abemaciclib) by Eli Lilly are currently approved to treat some kinds of breast cancer.
The investigators confirmed that treating SCCOHT cells with some of these inhibitors could prevent them from growing, and that, in particular, Ibrance could prevent SCCOHT tumor growth in a mouse model of the disease.
They also figured out why cells with mutated SMARCA4 are sensitive to these inhibitors — these mutations cause cells to produce less of the protein Cyclin D, which, in turn, leads to the CDK4/6 sensitivity.
Human SCCOHT samples were then analyzed and found to have these same genetic changes, whereas samples of another type of ovarian cancer — high-grade serous carcinoma — lacked these distinctive genetic changes.
These findings suggest that, much like the tumor cells in mice, tumors in humans are likely sensitive to CDK4/6 inhibitors. However, further clinical studies in humans will be needed to confirm this.
In addition, the researchers simultaneously published another study in the same journal that showed that these same genetic changes — and this same sensitivity to CDK4/6 inhibitors — might also be present in some cases of lung cancer, which is much more common than SCCOHT.
Therefore, previously approved breast cancer treatments may have benefits for patients with other cancer types, the researchers said, but further studies are needed.