Researchers Identify Effective Drug Treatment for Rare Ovarian Cancer

Overview of Small Cell Carcinoma of the Ovary

Small cell carcinoma of the ovary, known as SCCOHT, is a rare and highly aggressive tumor predominantly affecting young women, with a median diagnosis age of 24. Ovarian cancers represent approximately 3% of all cancers in women and stand as the fifth leading cause of cancer-related mortality among this demographic. Ovarian cancer is classified into various types based on the originating cell type.

Characteristics of Small Cell Carcinoma

SCCOHT accounts for about 0.1% of ovarian cancer cases, with long-term survival rates reaching 33% when diagnosed early. Notably, approximately two-thirds of women diagnosed with this cancer type experience hypercalcemia. The symptoms of SCCOHT are often similar to those of other ovarian cancers, including bloating, abdominal or pelvic pain, difficulty eating, early satiety, and urinary issues. Due to their subtle nature, these symptoms can delay diagnosis. Therefore, persistent symptoms lasting more than three weeks warrant medical evaluation.

Genetic Origins of SCCOHT

Monogenic Nature of the Cancer

Unlike most ovarian cancers with complex genetic causes, SCCOHT’s genetic origins can be traced back to mutations in a single gene known as SMARCA4. Researchers at McGill University, Canada, utilized this monogenic characteristic to identify druggable protein targets for treatment. Their preclinical findings were published in *Nature Communications*.

Collaborative Research Efforts

The study was a collaborative effort led by Dr. Sidong Huang and Dr. William Foulkes at McGill University, along with teams from the Ottawa Hospital Research Institute and the University of Michigan.

Inhibition of Enzymes to Combat Cancer Growth

Impact of CDK4/6 Inhibition

The research team discovered that inhibiting specific enzymes known as cyclin-dependent kinases 4 and 6 (CDK4/6) effectively halted the growth of SCCOHT cancer cells. Interestingly, these enzymes were found at lower levels in SCCOHT cells compared to other ovarian cancer types, yet they remained crucial for the cancer’s growth. Utilizing existing drugs approved for the treatment of a subtype of breast cancer, the team demonstrated that CDK4/6 inhibition could block SCCOHT cell proliferation in both laboratory-cultured cells and tumor cells extracted from patients.

Potential for Broader Drug Applications

Dr. Huang emphasized the significance of these findings, stating, “Our findings potentially broaden the applications of these drugs.”

Current Use of the Drug in Breast Cancer Treatment

Existing Clinical Safety

The CDK4/6 inhibitors are currently used in treating the ER-positive subtype of breast cancer, ensuring their clinical safety. Dr. Huang noted that identifying effective existing treatments could be a pivotal moment for patients facing SCCOHT, particularly since this rare cancer is unlikely to receive dedicated drug development. Furthermore, these inhibitors may also enhance anti-tumor immunity, as demonstrated in other cancer types.

Extension of Research to Other Cancers

The research team extended their investigation of SCCOHT cells to non-small cell lung cancer (NSCLC) cells and found that approximately 10% of NSCLC tumors lack functional SMARCA4 protein. The results of this extended study were also published in *Nature Communications*.

Future Directions for Research

These discoveries pave the way for further clinical studies and screenings for other cancers that might share genetic vulnerabilities associated with the SMARCA4 gene. Dr. Foulkes expressed optimism, saying, “The dream would be to cure these cancers, but any hint of a response would be a positive step forward, particularly since current treatments for women affected by SCCOHT have limited effectiveness.”

References

Xue Y, Meehan B, Macdonald E, Venneti S, Wang XQD, Witkowski L, Jelinic P, Kong T, Martinez D, Morin G, Firlit M, Abedini A, Johnson RM, Cencic R, Patibandla J, Chen H, Papadakis AI, Auguste A, de Rink I, Kerkhoven RM, Bertos N, Gotlieb WH, Clarke BA, Leary A, Witcher M, Guiot MC, Pelletier J, Dostie J, Park M, Judkins AR, Hass R, Levine DA, Rak J, Vanderhyden B, Foulkes WD, Huang S. CDK4/6 inhibitors target SMARCA4-determined cyclin D1 deficiency in hypercalcemic small cell carcinoma of the ovary. Nat Commun. 2019 Feb 4;10(1):558. Press release retrieved from https://www.sciencedaily.com/releases/2019/02/190204124203.htm