Oncogenic gene expression programs in leiomyosarcoma
Leiomyosarcoma Support and Direct Research Foundation (LMSDR), awarded a $85,000 research grant in 2018, to Dr. Matt Hemming at Dana Farber Cancer Institute to study leiomyosarcoma. Here is his letter sharing the progress of his research on LMS.
There are lots of reasons to be excited about this latest research update by Matt Hemming- research funded by the money that we raise to help fight Leiomyosarcoma.
Matt reports that they have further developed new “patient derived xenografts”, have profiled their genetic sequence and are planning to start trialling novel targeted therapies. In layman’s terms this means that human leiomyosarcoma cells have been transplanted and grown in lab mice and appear to behave just like our own tumors, giving a “valid model” of LMS that can be studied.. Sequencing the tumors allows researchers to find the genetic mutations that may be driving their cancerous growth , which gives possible targets for new treatments..
In addition they have studied the presence of circulating LMS DNA in the mice which may one day offer a way of detecting and monitoring LMS through blood testing
So- rather than extrapolating data from carcinomas like breast, or bladder cancer, or even data from other sarcomas, we have someone actually specifically studying the genes that drive leiomyosarcoma and there already plans to trial two new drugs on these mice.
Yes- human trials will still take time to come but this is at least a start, specific to LMS!
Thank you for reaching out, and we have made some significant progress since our last communication earlier this year! I shared a preliminary manuscript in February, and have been sharing the work with others in the field to try and galvanize interest in establishing a nomenclature and direction for future research. I’ve found the few labs I’ve reached out to have been entrenched in their own silos, but there is an upcoming LMS meeting next month I’ll present some of the work at and hopefully start the right conversation. The updated manuscript, with additional data and analysis from our last conversation, is here if you are interested: (manuscript omitted due to copyrights until published.)
The most advanced developments in our work (extensions of projects described in the proposal) focus on the evaluation of existing models and development of new patient derived xenografts (PDX). Since the proposal, we have developed and sequenced additional PDX models by RNA-seq. New from the proposal is performing cancer NGS profiling on them – sequencing >400 cancer associated genes and translocations – to help define these models. We have also performed low-passage whole genome sequencing to characterize chromosomal abnormalities in tumors and generations of PDX as they are serially passaged. This analysis includes identification of circulating tumor DNA in the mice, which might be a helpful treatment biomarker in future clinical trials and clinical care. Attached is a plot of one PDX where we have profiled copy number changes in the primary tumor, 17 generations of PDX (with tumor serially transferred from one mouse to another), and plasma – all indicating the fidelity of these models to the disease derived from the original LMS tumor.
Armed with these data, we reason that we have valid disease models and are now growing PDX for two drug trials using novel targeted therapies currently in human clinical trials. We have other ideas for therapy development in LMS from this work, but results from these two initial leads will help specify a direction to move forward in.
Please let me know if I can more formally provide an update, either in written form or by phone. I’m hopeful that presenting some of our work next month to an LMS-biased audience will spark interest in the models we’re developing and the language to describe this disease, and very hopeful that as the PDX treatment data arise they will be the best possible support for initiating a rational clinical trial for LMS. Thank you for your support!