LMS RESEARCH PROJECTS SUPPORTED BY THE NLMSF

 
NLMSF FUNDING SUPPORT FOR RESEARCH PROJECTS –   Through “investing” in LMS Research, patients, families, friends came together to support /contribute to our investment “gifts” directed to LMS research –  lighting the way to the discovery that can turn into clinical care treatment options . .  . “gifts” that keep giving!

“INVESTMENT”  CONTRIBUTIONS IN ACTION:

The Foundation is most appreciative for all researchers who submitted outstanding research proposal for consideration, signaling their deep interest moving LMS specific research forward.
 
This list begins with the most  recently funded research projects:
 
Congratulations to the NLMSF Research Grantees for 2023 and 2024
 
                                                                       
 
Joanna Pryzbyl, PhD.     
McGill University, Montreal,
Quebec, Canada                                            

Development of the Multi-Omic Liquid Biopsy Assay
for the Pre-Operative Diagnosis of Uterine
Leiomyosarcoma and Benign Leiomyoma

Priya Chudasama, Ph.D.
German Cancer Research Center
Heidelberg, Germany
 
Spatial Heterogeneity and Therapeutic Implications of
Activated Telomere Maintenance Mechanisms in
Leiomyosarcoma 
 
 

NLMSF Grant for 2022-2023:


 Matthew Hemming, M.D., Ph.D.
Dana Farber Cancer Institute/Harvard Medical School 

“We are so grateful to the National Leiomyosarcoma Foundation for supporting out research! This support will allow us to develop and interrogate much needed laboratory models of leiomyosarcoma. For this first time, we will be using high-throughput drug screening approaches in patient samples and xenograft models to identify novel and targeted therapies, which we aim to translate into novel clinical trials and treatment options for patients. This urgently needed work wouldn’t be possible without the support form NLMSF!

 

NLMSF Grant for 2021-2022:

Nicolas Llosa, MD
Johns Hopkins Cancer Center
 
The research project submitted by Dr. Llosa will take a deep dive into the microenvironment, the tumor biology and metabolism, and epigenetics, and  its impact on  LMS tumor cell biology – affecting immunotherapy progress. This is fine example of a project that holds great promise for the trajectory of LMS research focus for the future. 
 
This research project will focus on the following aims:
*  Define the molecular mechanisms that regulate the accumulation and pathologic activation of TIM (Tumor-infiltrating myeloid cells) present in Human LMS.
*  Decipher the phenotype and functional state of TIM responsible for T-cell suppression and enablement of 
   immune evasion in human LMS.
*  Determine whether metabolic inhibition of intra-tumoral myeloid-derived suppressor cells (MDSC) and reprogramming of tumor-associated macrophages (TAM) enhances antitumor immunity and tumor response
to checkpoint blockage in a 3D human model of LMS.   
 

ANNOUNCEMENT  OF THE GRANT TO DR. LLOSA AT THE 2020 CTOS ANNUAL MEETINGBY THE NLMSF EXECUTIVE COMMITTEE MEMBER

 
 

2019

CANCER CELL LINE PROJECT / Dependency Map Project –  BROAD INSTITUTE OF MIT/HARVARD

 

The Leiomyosarcoma Cancer Cell Line Project:
2019 Announcement by the Broad Institute of MIT/Harvard
 
THE BROAD INSTITUTE OF MIT/HARVARD ANNOUNCES: “We are pleased to announce an expansion of the partnership between the Broad Institute’s Dependency Map team and the National Leiomyosarcoma Foundation (NLMSF) to create a publicly-accessible, genomically characterized collection of cell line models of LMS and to use these models to hunt for new drug targets and repurposing opportunities.”  This is a research initiative to further amplify global LMS research efforts  (3 year project)
 
 
 
SARCOMA ALLIANCE THROUGH RESEARCH AND COLLABORATION (SARC)
SARC-LMS Research Consortium Project  – A group of three LMS-specific research projects currently in progress. 
 
 
             
 
 
 
 Image result for huntsman cancer institute      Patient Education | National LeioMyoSarcoma Foundation
·         The Foundation supports the new research initiative for the P53  – the study of potentially targetable mutations –  p53, with 10 additional elements that can be applied to LMS.  The role of macrophages in tumor microenvironment for LMS – Anti-PD1 investigational research, comparing macrophages in LMS vs breast and colon cancer is beginning.  Development of new antibody vs macrophage in combination with anti-PD-1 antibody is being investigated (Pembrolizumab and Optivo);  validation of LMS cell lines and PDX models and SARC trial patients to search for targeted tumor signatures;  identification of such tumor search signatures will benefit P13/mTOR, p53, LGF1R, ER therapies.

The Specialized Program of Research Excellence (SPORE), a Sarcoma Alliance Through Research and Collaboration research project for new biologically-rational clinical trials in sarcoma, that hold promise for cross over progress in a variety of sarcoma subtypes, including
LMS.  Evaluating patient response through a multidisciplinary approach to the evaluation of patient response to current treatment therapies continues to facilitate exploration of new/ more effective treatment options, and promotes the acceleration of treatment advancements for the full spectrum of the sarcoma population. 
 
           Cancer Center | Stanford Health Care           
 
Development of a non-invasive diagnostic assay for the highly accurate pre-operative distinction between uterine leiomyomas and leiomyosarcomas.  The detection of circulating tumor DNA reported in several cancers, but only a few in sarcomas and no large-scale study to detect ctDNA for LMS patients –inspired further study for sarcomas and brought proof of principle study to include LMS patients to determine the feasibility of ctDNA analysis. Such
an analysis would enable clinicians to identify patients who could safely undergo laparoscopic procedures using power morcellators.  A “liquid biopsy” test based on the analysis of tumor-associated genetic aberrations in circulating tumor DNA (ctDNA) in plasma maybe of great use such situations.
 

 2016
Maximizing Therapeutic Response in Leiomyosarcoma:

The Liddy Shriver Sarcoma Initiative coordinated the funding support for a $1 million international collaborative grant (Co-funded by the NLMSF) focusing on leiomyosarcoma (LMS). Investigators from France, Germany, and the United States joined forces in this 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. .
Patient Education | National LeioMyoSarcoma Foundation
 
 
 Dr. Matt Van de Rijn’s Circulating Tumor DNA / ctDNA research project summary:
Cancer Center | Stanford Health Care
Circulating tumor DNA (ctDNA) 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.
 
 
 
 
2015

 Gonzalo Lopez, Ph.D. of the Solove Cancer Institute, James Cancer Center, Ohio State University.  Dr. Lopez’s study is  summarized as follows:
 
Study summary: 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.”
 
 The National SARC Sarcoma SPORE renewal application submitted by Dr. Jonathan Fletcher, Dana Farber Cancer Institute Brigham and Women’s Hospital, Boston, MA: Funding support by the NLMSF
This project is in 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. 
 
 The research study by Dr. Khandan Keyomarsi, Ph.D., Dr. Kelly Hunt, MD
MD Anderson Cancer Center, Houston, TX:
Patient Education | National LeioMyoSarcoma Foundation
This project 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.
 
*  MELATONIN Research with Dr. Bob Dauchy, PhD.
              Department of Structural and Cellular Biology,  TULANE University
    1. Robert Dauchy studies Planetary Geology, Human Factors in Aviation, and Aviation History (Transport History). … experimental cancers in vivo is inhibited by either physiological or pharmacological levels of the pineal gland hormone melatonin, although the. … Robert T. Dauchy, Eugene W. Holowachuk. and Mary S. Ruhoff Bassett Research …
  1. Antineoplastic effects of melatonin on a rare malignancy of mesenchymal origin: melatonin receptor-mediated inhibition of signal transduction, linoleic acid metabolism and growth in tissue-isolated human leiomyosarcoma xenografts. … Address reprint requests to Robert T. Dauchy, Laboratory of Chrono-Neuroendocrine Oncology, Department of 

THE NLMSF SUMMARY OF RESEARCH FUNDING SUPPORT SINCE THE BEGINNING . . .  . .

Patients and their Families came together in 1997 to form the “HUGFEST” – a forerunning to what is now the National Leiomyosarcoma Foundation, incorporated in 2002.
 
The Foundation is a most careful steward of acquired contributions/donations/gifts directed to research, with operational expenses at 1.7%  in 2018..
 
As of 2002, the NLMSF has always directed donations to important and well-vetted research projects, felt to hold promise for future advancement in hopeful breakthroughs for treatment acceleration   The NLMSF Medical Advisory Council is charged with the review of incoming research projects for funding.
 
The history and momentum of the gracious contributions made by the LMS Community each year is reflected in the momentum of Foundation support for approved research projects.
2002
University of Pennsylvania Hospital
 
2004
University of Pennsylvania Hospital
 Correl Institute for Medical Research
 
2005
University of Pennsylvania Hospital
LMS Tissue Repository established by Dr. Brooks.
 
Stanford University – Dr. M. van de Rijn
 
2006 
Stanford University –  Dr. M. van de Rijn
 
2007
Basset Research Institute – Dr. D. Blask
Stanford University –  Dr. M. van de Rijn
 
2008
Mount Sinai School of Medicine – Dr. J. Martignetti
 
Stanford University – Matt van de Rijn, M.D., Ph.D.
 
2009  
Stanford University – Dr. M van de Rijn
 
2010
Stanford University – Matt van de Rijn, M.D., Ph.D.
2011
Tulane University School of Medicine – Dr. D. Blask
 
Stanford University – Matt van de Rijn, M.D., Ph.D.
 
2012
Tulane University School of Medicine – Dr. D. Blask / Dr. L. Mao
2013
Stanford University – Matt van de Rijn, M.D., Ph.D.
 
2014
Stanford University –  Matt van de Rijn, M.D., Ph.D.
 
2015 
Ohio State University  James Cancer Center
 G. Lopez, Ph.D.
 
Stanford University – Matt van de Rijn, M.D., Ph.D.
 
2016
 
International Collaborative LMS Grant  – co-funding through
 the coordination of L. Shriver Initiative
Drs. Bauer, Chibon, Fletcher, Langenau, van de Rijn
 
MD Anderson Cancer Center, Drs. K. Keyomarsi and K. Hunt
( 2 year project)
2017
MD Anderson Cancer Center – Drs Keyomarsi  and K. Hunt
 

Stanford University –  Matt van de Rijn, M.D., Ph.D.

2018
SARC – SPORE Grant (Sarcoma Alliance Through Research Collaboration)
(bridge grant)
 
Stanford University – Matt van de Rijn, M.D., Ph.D.
 
SARC – LMS Specific research project
 
2019
Broad Institute – LMS CELL LINE PROJECT  (3 year project)
 
 
SARC –  LMS specific research
RESEARCH  THINK-TANK FUNDING:
 
NLMSF – SPAEN International LMS Research Roundtable Conference
 
 
WHAT AN AMAZING IMPACT YOUR “INVESTMENT” 
 DONATIONS ARE MAKING!