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:
This list begins with the most currently funded research projects:
2020 – 2021 FUNDED RESEARCH PROJECTS:
Nicolas Llosa, MD
Johns Hopkins Cancer Center
CTOS ANNOUNCEMENT BY THE NLMSF EXECUTIVE COMMITTEE MEMBER:
:Dr. Seth Pollack’s Grant Presentation at CTOS
Congratulations to Dr.Nicolas Llosa, MD, Johns Hopkins Cancer Center, for a most promising research strategy, with the funding support of the NLMSF for 2021-2022. Dr. Llosa is now one of three newest members to the NLMSF-SPAEN International LMS Research Roundtable.
Dr. Matthew Hemming – Dana Farber / Harvard Medical School – 2021 Recipient of the
NLMSF Grant for 2022-2023:
“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!
The selected 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. 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 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.
* 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. Mid-term reporting by Dec. 31, 2021.
to checkpoint blockage in a 3D human model of LMS. Mid-term reporting by Dec. 31, 2021.
CANCER CELL LINE PROJECT / Dependency Map Project – BROAD INSTITUTE OFMIT/HARVARD
* Support LMS cell lines going forward to CrisprCas9 genomic profiling and repurposed drug screening.
* Connecting with the NLMSF – SPAEN International LMS Research Roundtable for Workgroup collaborative assistance for LMS cell lines and PDX models.
* Expansion of a functional genomics platform for rare soft tissue sarcoma, that include leiomyosarcoma as one of the selected sarcoma subtypes for this purpose.
SARCOMA ALLIANCE THROUGH RESEARCH AND COLLABORATION (SARC)
SARC-LMS Research Consortium Project – A group of three LMS-specific research projects currently in progress.
The 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
* PHASE 2 Pazopanib / TRC 105 – Clinical Trial Study – MOFFIT CANCER CENTER
Pazopanib with first-line therapy of anthracycline or gemcitabine. Estimation of progression-free survival with advanced leiomyosarcoma;
estimation of overall response with patients with uterine LMS pazopanib and TR 105 antibody. Determination of frequency and severity of adverse events; characterize the pharmacokinetic profile of TRC105 and pazopanib and the formation of TRC 105 anti-product antibodies; exploration of the correlation of efficacy of the progression-free survival and overall response.
· 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.
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.
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.
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.
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. This is a 2-year project. Co-funding by the NLMSF.
Dr. Matt Van de Rijn’s Circulating Tumor DNA / ctDNA research project summary:
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.
Dr. 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 application submitted by Dr. Jonathan Fletcher, Dana Farber Cancer Institute Brigham and Women’s Hospital, Boston, MA:
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. Co-funding by the NLMSF.
The research study by Dr. Khandan Keyomarsi, Ph.D., Dr. Kelly Hunt, MD
MD Anderson Cancer Center, Houston, TX:
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
- 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 …
- 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 – Dr. M. van de Rijn
2009
Stanford University – Dr. M van de Rijn
2010
Stanford University -Dr. M. van de Rijn
2011
Tulane University School of Medicine – Dr. D. Blask
Stanford University – Dr. M. van de Rijn
2012
Tulane University School of Medicine – Dr. D. Blask / Dr. L. Mao
2013
Stanford University – Dr. M van de Rijn
2014
Stanford University – Dr. M. van de Rijn
2015
Ohio State University James Cancer Center
Dr. G. Lopez
Stanford University – Dr. M. van de Rijn
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 – Dr. M. van de Rijn
2018
SARC – SPORE Grant (Sarcoma Alliance Through Research Collaboration)
(bridge grant)
Stanford University – Dr. M. van de Rijn
SARC – LMS Specific research project
2019
Broad Institute – LMS CELL LINE PROJECT (3 year project)
Moffitt Cancer Research Institute – Dr. M. Druta
(2 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!
DONATIONS ARE MAKING!