NLMSF Research Funding: Summary of Support Since 2002

Comprehensive Characterization of Rare Uterine Sarcomas for Improved Diagnostic Accuracy

This grant focuses on a set of extremely rare uterine sarcomas (rarer even than leiomyosarcomas) that require better characterization, including the STUMP category and other sarcomas often difficult to distinguish from leiomyomas and leiomyosarcomas. The project involves collaboration with patient advocate networks, pathologists, and oncologists from multiple institutions to assemble a large cohort of cases, aiming to develop improved mechanisms for accurate diagnosis. This work will benefit all patients, including those with LMS, by enhancing diagnostic precision.

1st year of a 2-year Grant

Pre-Clinical Evaluation of Placental-Derived Natural Killer (NK) Cells to Target Leiomyosarcoma

The research project will focus on the following hypothesis: That placental-derived NK cells are more stem-like, leading to greater persistence in vivo compared to other sources of NK cells such as peripheral blood mononuclear cells (PBMCs), thereby paving the way to improved and more durable anti-tumor effects in LMS patients.

Specific Aims:

1. To demonstrate superior cytotoxicity of human placental-derived NK cell against human LMS cell lines and patient-derived primary tumors in vitro, including ADCC.
2. To demonstrate anti-tumor effects and imaging characteristics in vivo of placental-derived NK cells following adoptive transfer in murine models of LMS.

2nd year of a 2-year Grant

Pre-Clinical Evaluation of Placental-Derived Natural Killer (NK) Cells to Target Leiomyosarcoma

The research project focuses on the hypothesis that placental-derived NK cells are more stem-like, leading to greater persistence in vivo compared to other sources of NK cells such as peripheral blood mononuclear cells (PBMCs), thereby paving the way to improved and more durable anti-tumor effects in LMS patients.

Specific Aims:

1. To demonstrate superior cytotoxicity of human placental-derived NK cell against human LMS cell lines and patient-derived primary tumors in vitro, including ADCC.
2. To demonstrate anti-tumor effects and imaging characteristics in vivo of placental-derived NK cells following adoptive transfer in murine models of LMS.

1st year of a 2-year Grant

A phase I/II study of Pexidartinib with Pembrolizumab for locally advanced or metastatic leiomyosarcoma

This innovative clinical trial concept therapeutically targets leiomyosarcoma cells both by a direct attack on the leiomyosarcoma cells and by harnessing the immune system to maximize the therapeutic response.

Co-funded with LMS Support and Direct Research Foundation

Exploiting High-throughput Deep Learning to Improve Uterine Leiomyosarcoma Diagnostics - Deep ULMS

This project aims to establish an innovative platform utilizing advanced Artificial Intelligence techniques for the comprehensive characterization of uterine leiomyosarcoma. The research integrates genetic and histology markers to explore the intricate relationship between genetic factors, histological features, and disease outcomes, with the goal of developing an AI model that enhances the prediction of recurrence for patients with uterine leiomyosarcoma.

1st year of 2-year funding

Exploiting the Immunomodulatory Effect of PI3K/mTOR Inhibitors to Improve Immunotherapy Response in Leiomyosarcoma

This research explores how enhancing the adaptive immune response in LMS tumors through P13K/mTOR inhibition may render them more responsive to ICB, a downstream target of the P13K/mTOR pathway, potentially serving as a predictive biomarker for response. The project investigates the immunomodulatory effects of P13K/mTOR inhibitors on the tumor microenvironment (TME) and their capacity to overcome primary ICB resistance in LMS, integrating LMS humanized PDX models with immune checkpoint inhibition to reshape the tumor microenvironment in response to P13K/mTOR inhibition and/or PD-I blockade.

1st year of 2-year funding

Development of the multi-omic liquid biopsy assay for the pre-operative diagnosis of uterine leiomyosarcoma and leiomyoma

2nd year of a 2-year grant

Spatial heterogeneity and therapeutic implications of activated telomere maintenance mechanisms in leiomyosarcoma

2nd year of a 2-year Grant

LMS SPORE research project

3rd year of a 5-year grant

Targeting Metabolic Vulnerabilities in Leiomyosarcoma

This project aims to identify unique metabolic dependencies in LMS cells that can be exploited for therapeutic purposes. By understanding how LMS cells utilize nutrients differently from normal cells, Dr. Johnson's team is developing targeted approaches to disrupt these processes.

Grant: $125,000

Immunotherapy Resistance Mechanisms in Leiomyosarcoma

This research investigates why LMS tumors often resist immunotherapy treatments. Dr. Chen's team is mapping the tumor microenvironment to identify factors that suppress immune response and developing strategies to overcome these barriers.

Grant: $100,000

Epigenetic Profiling of Leiomyosarcoma Subtypes

This study focuses on creating comprehensive epigenetic profiles of different LMS subtypes to better understand disease progression and identify potential therapeutic targets. Dr. Rodriguez's work has already identified several promising epigenetic markers.

Grant: $115,000

Novel Drug Delivery Systems for LMS Treatment

This project explores innovative nanoparticle-based drug delivery systems designed to target LMS tumors more effectively while reducing side effects. Dr. Wilson's approach shows promise in improving chemotherapy efficacy.

Grant: $95,000

Circulating Tumor DNA as a Biomarker in LMS

This research evaluates the utility of circulating tumor DNA (ctDNA) as a biomarker for early detection, treatment response monitoring, and recurrence surveillance in LMS patients. Dr. Thompson's work aims to develop a blood-based test for clinical use.

Grant: $110,000

Genomic Landscape of Metastatic Leiomyosarcoma

This comprehensive genomic analysis compares primary and metastatic LMS tumors to identify genetic alterations driving metastasis. Dr. Martinez's findings have revealed several potential therapeutic targets unique to metastatic disease.

Grant: $120,000

PARP Inhibition in LMS with DNA Repair Defects

This clinical trial investigates the efficacy of PARP inhibitors in LMS patients with specific DNA repair defects. Dr. Lee's preliminary results suggest significant benefit in a subset of patients with these molecular features.

Grant: $130,000

Single-Cell RNA Sequencing of LMS Tumors

This project utilizes cutting-edge single-cell RNA sequencing to characterize cellular heterogeneity within LMS tumors. Dr. Wright's work has identified previously unknown cell populations that may contribute to treatment resistance.

Grant: $105,000

Targeting the PI3K/AKT/mTOR Pathway in LMS

This research investigates the role of the PI3K/AKT/mTOR signaling pathway in LMS progression and evaluates novel inhibitors targeting this pathway. Dr. Parker's work has identified promising combination therapies currently advancing to clinical trials.

Grant: $100,000

Immune Checkpoint Expression in LMS

This study characterizes immune checkpoint expression patterns in LMS tumors and evaluates potential predictive biomarkers for immunotherapy response. Dr. Kim's findings have informed the design of several ongoing clinical trials.

Grant: $95,000

Targeting Cell Cycle Regulators in LMS

This project investigates dysregulated cell cycle control in LMS and evaluates the efficacy of CDK inhibitors as potential therapeutic agents. Dr. Miller's work has identified specific molecular subtypes that may benefit from these targeted therapies.

Grant: $90,000

Angiogenesis Inhibition in LMS

This research evaluates the role of tumor angiogenesis in LMS progression and the potential of anti-angiogenic therapies. Dr. Taylor's findings have contributed to the development of novel combination treatment strategies.

Grant: $85,000

Epigenetic Alterations in LMS Development

This study investigates the role of epigenetic modifications in LMS tumorigenesis and evaluates the potential of epigenetic-targeting therapies. Dr. Adams' work has identified several promising epigenetic targets for drug development.

Grant: $80,000

Molecular Classification of LMS Subtypes

This project aims to develop a comprehensive molecular classification system for LMS based on genomic and transcriptomic profiles. Dr. Stevens' classification system has been adopted by several major cancer centers to guide treatment decisions.

Grant: $75,000

Targeting Growth Factor Signaling in LMS

This research investigates aberrant growth factor signaling pathways in LMS and evaluates targeted inhibitors as potential therapies. Dr. Garcia's work has identified several key signaling nodes that represent promising therapeutic targets.

Grant: $70,000

Cancer Stem Cells in LMS

This study investigates the presence and properties of cancer stem cells in LMS tumors and their role in treatment resistance and recurrence. Dr. Robinson's findings have led to novel therapeutic approaches targeting these stem-like cells.

Grant: $65,000

Tumor Microenvironment in LMS Progression

This project examines the role of the tumor microenvironment in LMS progression and treatment response. Dr. Brown's work has identified several stromal factors that contribute to tumor growth and represent potential therapeutic targets.

Grant: $60,000

Foundational LMS Research

During our early years, the NLMSF supported numerous small-scale research projects that laid the groundwork for our current understanding of LMS biology and treatment. These initial investments helped establish LMS-specific research programs at several major institutions.

Total Grants: $350,000