In 2018 and 2019, Leiomyosarcoma Support & Direct Research Foundation (LMSDR) awarded Dr. Mathew Hemming MD PhD of Dana Farber a grant totaling $84,000 for his two-year project: “Exploring Leiomyosarcoma Functional Genomics to Identify Disease Specific Vulnerabilities.”
Below is Dr. Hemming’s letter to LMSDR and the LMS patient community to update us all on his very important work on leiomyosarcoma.
Thank you so much for your support the past two years, and your interest in supporting our work going forward! I’m really excited by what we’ve been able to accomplish, and I’m hoping results make it to publication and begin helping to shape our translational approach to LMS this year. Here is a brief summary of the primary research efforts:
- Understanding the transcriptional landscape of LMS: Unlike many other cancers, LMS lacks recurrent activating mutations in genes that cause cancer. By contrast, LMS is characterized by loss of tumor suppressor genes (RB1, P53, PTEN) that normally prevent cancer from starting. However, we understand very little about which genes are then responsible for controlling the growth of LMS. The goal of this project is to study the gene expression program of LMS tumors and cell lines to identify gene dependencies, biomarkers, and potential vulnerabilities in LMS.
- Understanding chromatin organization in Leiomyosarcoma: Though LMS characteristically has multiple amplified and deleted genes throughout the tumor’s genome, each tumor must maintain a functional organization of the genes most important to tumor biology. The goal of this project is to define the chromatin landscape of LMS to identify these regions of the genome most important to LMS, and use this information to better understand LMS biology.
- Developing Patient Derived Xenografts (PDX) of Leiomyosarcoma: As we identified in project #1, our existing LMS cell lines do not adequately model the human disease, and may hold little value in preclinical research. Thus, there is a great need for preclinical models that have fidelity to the human disease. To this end, we have developed several PDX models which very closely mirror their tumor of origin. We have characterized these models through histology, transcriptional profiling, mutational analysis and copy number changes. We are now actively treating these mouse models in preclinical trials using candidate drugs that may translate directly into clinical trials for LMS patients.
I hope this was a helpful summary, and please let me know if I can expand on any point! This work work not have been possible without the support of your team, and my goal (and all of our goals) is to push this and other work towards clinical relevance and new diagnostics and treatments as soon as possible.
Thank you again and best wishes,
If you would like to help encourage and sponsor more research on leiomyosarcoma, please donate to Leiomyosarcoma Support & Direct Research Foundation. We are a 501(C)(3) nonprofit charity.