Leiomyosarcoma and Endometrial Stromal Sarcoma Research Under the Direction of Drs. Robert West and Matt Van de Rijn at Stanford University

Stanford has developed a new technique called 3SEQ to determine expression levels for all human genes in tumor samples. The novel aspect of this technology is that it is possible to use paraffin embedded tissue and it does not require fresh frozen tissue. The latter is often difficult to obtain especially for rare tumors such as uterine sarcomas. Stanford has obtained funding through an NIH RO1 grant and through BeatSarcoma to study leiomyosarcomas (the most common form of uterine sarcoma) and has used the funding for a study a number of uterine leiomyosarcomas (LMS) as a follow-up to its recent paper in Oncogene. Stanford is still in the process of collecting additional samples but preliminary data analysis has begun. Stanford expects that over the next years it will study about 200 LMS cases in this manner. This is not an unrealistic expectation as it already has identified 60 cases from Stanford alone and is in addition collaborating with Dr. Chris Fletcher who already has sent another 25 cases.

Stanford is now also in the process of analyzing a significant number (paraffin blocks for ten cases so far have been identified) of endometrial stromal sarcomas (ESS). ESS is the second most common sarcoma of the uterus and BeatSarcoma will help fund this important aspect of our research. The hope is that by comparing LMS to ESS and to normal uterine tissue Stanford will be able to develop better diagnostic tools to separate these tumors and to develop novel potential therapeutic targets for each.

UCSF Sarcoma Research, led by Dr Eric Nakakura

Dr. Eric Nakakura is a surgeon-scientist who specializes in the treatment gastrointestinal neuroendocrine tumors and soft tissue sarcomas, including tumors of the retroperitoneum, trunk and extremities. As a member of the UCSF Helen Diller Family Comprehensive Cancer Center and the Gastrointestinal (GI) Oncology Research Program, he also conducts research into basic sarcoma biology.

As a sarcoma surgeon, Dr. Nakakura has ongoing, direct access to human sarcoma samples from resected specimens. In collaboration with the laboratory of Dr. Kevin Shokat, the GI Oncology Research Program has had success using a new model of animal studies that makes use of excess tumor tissue following resection. Using state-of-the-art techniques, they are implanting these human tumors in mice. Researchers have found that this model more accurately represents the growth of human cancers than trying to grow the samples in the culture dish, which can change the character of the cancer specimens. This is a powerful tool in helping identify which therapies might be most effective for individual patients, and to identify possible vulnerabilities in cancer stem cells.

Currently, due to BeatSarcoma funding, research is underway to determine the role of the mTOR pathway as it relates to sarcoma growth. Prior investigations focused on studying the role of the mTOR pathway in neuroendocrine tumors found this to be an important signaling pathway and researchers hypothesize it may be responsible for sarcoma growth.

As a result of BeatSarcoma’s initial investment of $5,000, Dr. Nakakura and his colleagues have been able to advance their studies at the UCSF Helen Diller Family Comprehensive Cancer Center in the battle against sarcoma. A major challenge in sarcoma research is a paucity of models to study the disease and to develop new therapies. In order to develop new models to study this rare disease, researchers take limited samples obtained from patients undergoing surgical resection at UCSF. These limited samples are immediately implanted into immunodeficient mice, which provide a permissive environment for the growth and expansion of small amounts of sarcoma tissue.

Dr. Nakakura and his colleagues have successfully established these so called “sarcoma xenografts” from two patients and are planning to use them to develop new cell lines. New sarcoma xenografts and cell lines will be invaluable models to evaluate new treatment strategies. One strategy currently being evaluated at UCSF is targeting the mTOR pathway, a critical regulator of cell growth. Researchers have successfully optimized the conditions to measure mTOR pathway activity in human samples. With the continued partnership of BeatSarcoma, Dr. Nakakura and his colleagues will be able expand their analysis of the mTOR pathway in human sarcoma. Moreover, it will help determine if mTOR inhibition with drugs that target this pathway affect sarcoma growth and progression using these novel models.