New Finding Holds Promise for Future Targeted Treatment of Ovarian Cancer

Using sophisticated gene sequencing methods, researchers at Yale School of Medicine have demonstrated a regulatory link between stem cell factors that fuel the growth of ovarian cancer and the prognosis of patients, according to a new report.¹ The authors explain that this newly discovered link may be the foundation for the development of novel targeted ovarian cancer treatments.

Specifically, researchers found that stem cell factor Lin28 binds to the signaling molecule bone morphogenic protein 4 (BMP4) messenger RNA in epithelial ovarian cancer cells, which promotes the expression of BMP4 at the post-transcriptional level. In addition, the researchers found that high levels of Lin28 generally indicate an unfavorable prognosis when co-expressed with high levels of Oct4, another stem cell factor that has been implicated in the cancer stem cells of ovarian carcinomas.

These findings connect 2 ideas-termed the “cancer stem cell” and the “seed and soil” concepts-that are revolutionizing cancer treatment, explained the study authors in a press release from Yale University.² The cancer stem cell concept refers to the idea that a small subset of tumor cells, which are difficult to identify, fuel the growth of the bulk of the tumor. The predictive value of this concept is that ordinary cancer treatments will kill most of the tumor cells but leave behind cancer stem cells, which allow for continued tumor growth. The seed and soil concept refers to the role of the microenvironment of the tumor cells, which is simply the special environment needed for cancer cell growth and spread.

“Both concepts have particular relevance for the treatment of adult solid tumors, such as ovarian cancer, which has been notoriously difficult to diagnose and treat,” said coauthor Nita J. Maihle, MD, professor in the department of obstetrics, gynecology, and reproductive sciences at Yale School of Medicine and a member of Yale Cancer Center. “Ovarian cancer patients are plagued by recurrences of tumor cells that are resistant to chemotherapy, ultimately leading to uncontrolled cancer growth and death.”

The researchers go on to explain that the latest molecular ovarian cancer prognosis data support these results, suggesting that the tumor microenvironment plays an active role in ovarian carcinogenesis. “Together, these studies reveal new targets for the development of cancer therapies,” write the researchers.

Pertinent Points:
- A key link between stem cell factors that promote ovarian cancer growth and the prognosis of patients has been identified.
- This new finding indicates that targeted ovarian cancer therapies may be within reach.

References:

1. Ma W, Ma J, Xu J, et al. Lin28 regulates BMP4 and functions with Oct4 to affect ovarian tumor microenvironment. Cell Cycle. Dec 19, 2012;12(1). [Epub ahead of print.]
2. Ovarian cancer stem cell study puts targeted therapies within reach. Available at: http://medicine.yale.edu/news/article.aspx?id=4581. Accessed January 7, 2013.