LMS RESEARCH PROJECTS SUPPORTED BY THE NLMSF
1.Maximizing Therapeutic Response in Leiomyosarcoma
August 8, 2016 – The Liddy Shriver Sarcoma Initiative coordinated the funding support for a $1 million international collaborative grant focusing on leiomyosarcoma (LMS). Investigators from France, Germany, and the United States joined forces in the two-year research project, with the focus of identifying new therapies and for promising clinical trials for the most common and clinically challenging types of LMS. Co-funding by the NLMSF.
Read the study’s experimental plan: maximising therapeutic response to leiomyosarcoma
2. Dr. Matt Van de Rijn’s Circulating Tumor DNA / ctDNA research project summary:
Circulating tumor DNA 9ctDNA) can be measured in the blood of patients with a range of cancers such as lung carcinoma. Much less is known about the possibility to do this for sarcoma patients. In the past 2 years, Dr. Joanna Przybyl and Dr. Van de Rijn have applied two separate technologies to detect circulating tumor DNA in leiomyosarcoma patients.
This work was done in collaboration with the laboratories of Drs. Max Diehn and Ash Alizadeh at Stanford, and Dr. Marie Debiec-Richter at Leuven University in Belgium.
They were able to demonstrate that these technologies, previously set up to work for other cancer types by collaborators, can actually be applied to leiomyosarcoma as well. Therefore ctDNA can be quantified in the blood of LMS patients.
There is still progress to be made for applying this as a test in the clinic, however, and the next 1 – 2 years will be the devoted validation of the findings in a larger series of samples obtained from LMS patients. In addition, another project to determine whether there might be a capability to distinguish circulating DNA from uterine LMS from that DNA that is derived from benign uterine leiomyomas will begin. Funding by the NLMSF.
3. Dr. Gonzalo Lopez, Ph.D. of the Solove Cancer Institute, James Cancer Center, Ohio State University. Dr. Lopez’s study is summarized as follows:
RESEARCH ARTICLE Mocetinostat combined with gemcitabine for the treatment of leiomyosarcoma: Preclinical correlates
This study demonstrates the efficacy of mocetinostat (class I HDAC inhibitor) combined with gemcitabine in leiomyosarcoma (LMS) cell lines and an LMS xenograft mouse model. Resources to study LMS in vitro are limited; also in this study, we have established and utilized novel human LMS cell lines: Leio-012, Leio-196A, and LMS-117. Funding by the NLMSF.
Per Dr. Lopez:
“We are currently conducting a preliminary study on seeing if there is an impact on inhibiting isoform-specific HDACs in LMS.
We are also working on an article on sarcoma patient-derived xenograft (PDX) models which include LMS.”
4. The National SARC Sarcoma SPORE application submitted by Dr. Jonathan Fletcher, Dana Farber Cancer Institute Brigham and Women’s Hospital, Boston, MA, is in the review by the NIC/NCI, The project focus involves the commitment to support strategic pilot programs that discover new therapeutic targets in sarcoma. This pilot project and career development programs have enabled groundbreaking advances which have led to new clinical trials in sarcoma and enabled young physician-scientists to devote their careers to sarcoma research.
The pilot research project involves pooling national research and clinical strengths toward better therapies for sarcoma. The NIH/NCI feel that this will be a model for progress in rare diseases. Co-funding by the NLMSF.
5. The research study by Dr. Khandan Keomarsi, Ph.D., MD Anderson Cancer Center, Houston, TX, is designed to answer the question of whether the sequential application of chemotherapy agents currently being used have more promise than short duration cdk4 inhibitors alone. Analysis of proliferation indices and biologic effects (mitotic escalation) before, during, and after PD with AD by immunohistochemical analysis, protein extracts to demonstration target inhibition. Applying this to untreated tumors will help determine how the combination is working. Also, additional work will address whether the number of cycles of treatment improves outcome. There is a new arm to this study for 2018 and 2019 to support. Co-funding by the NLMSF.