A key link between stem cell factors that fuel ovarian cancer’s growth and patient prognosis has been identified, and a connection has been identified between two concepts that are revolutionizing cancer treatment.

The first concept is the idea of cancer stem cells, which suggests that at the heart of every tumor is a small subset of difficult-to-treat tumor cells that fuel the growth of the bulk of the tumor. This concept predicts that ordinary therapies typically kill the bulk of tumor cells while leaving a rich environment for continued growth of the stem cell tumor population.

The second concept, called seed and soil, defines a critical role for the microenvironment of the tumor cells. This is the special environment required for cancer cell growth and spread.


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“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 the study’s coauthor Nita J. Maihle, PhD, 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.”

In this study, a molecular basis for the interplay between these two concepts in ovarian cancer was defined. Sophisticated gene sequencing methods were used to demonstrate a regulatory link between the stem cell factor Lin28 and the signaling molecular bone morphogenic protein 4 (BMP4).

“These results are supported by the latest molecular ovarian cancer prognosis data, which also suggest an active role for the tumor microenvironment in ovarian carcinogenesis,” said lead author Yingqun Huang, MD, of Yale School of Medicine, and Maihle. “Together these studies reveal new targets for the development of cancer therapies.

This research was published in Cell Cycle (2013;12[1]:88-97).