Completed Grants and Sponsored Research

This project examines the hypotheses that Ewing sarcoma is dependent on ITGB2 signaling, that adhesion molecules are critical for the development of metastasis, and that Aurora B kinase inhibition could be a potent targeted approach for combination therapy with FAK inhibition in the treatment of Ewing sarcoma.

The goal of this project is to detect circulating tumor DNA levels in patients with Ewing sarcoma who were enrolled on a phase I study and correlate levels with treatment responses.

The goal of this project is to detect circulating tumor DNA levels in patients with leiomyosarcoma who were enrolled on a multi-institutional prospective trial and determine whether levels correspond to outcomes.

The major goal of this project is to validate the measurement of circulating tumor DNA assays (also known as liquid biopsies) obtained from blood samples as a biomarker of poor outcome for patients with Ewing sarcoma. We believe the results of this study could radically change the way we treat patients with the most aggressive form of this disease.

In this proposal, we aim to validate a new assay that detects tumor DNA from peripheral blood draws as a surrogate for tumor burden.

The major goals of this project are to perform preclinical testing of FAK inhibition using in vivo models of tumor progression and metastasis, to determine effective combinations of therapy with FAK inhibition in the treatment of Ewing sarcoma, and to determine which integrins are necessary for growth, transformation, and FAK activation in Ewing sarcoma.

The aims of this project are: (1) Does STAG2 and TP53 immunohistochemical staining successfully identify tumors with deleterious mutations in these genes? (2) Is STAG2 loss, alone or in combination with TP53 alteration, predictive of poor outcome inpatients with localized disease? (3) Does STAG2 loss occur more commonly in patients who present with metastatic disease?

The major goals of this project are to validate TranSS-Seq assay for detection of targeted sarcoma translocations in patient plasma; to correlate tumor-derived cfDNA level at diagnosis with outcome in cases of translocation-positive pediatric sarcomas; to correlate tumor-derived cfDNA levels over time with clinical course in translocation­positive pediatric sarcomas.

The major goals of this project are to perform the preclinical studies necessary to validate the use of FAK inhibition as a therapeutic approach to prevent disease progression and metastasis. Our approach will include testing the use of anti-Ewing chemotherapy and other targeted agents in combination with FAK inhibition to identify the most promising combinations. We also will utilize a genetic screening approach to find new therapeutic targets that may cooperate with FAK activity in Ewing sarcoma.

The major goals of this project are to complete the necessary preclinical studies to bring a FAK inhibitor to clinical trials for children with Ewing sarcoma; to determine if there is a role for this treatment approach in the prevention of metastatic disease; to nominate synergistic therapeutic combinations for future trials, and to identify additional adhesion molecules that play a role in the pathogenesis of Ewing sarcoma and activate FAK.

The major goals of this project are to perform preclinical testing of FAK inhibition using in vivo models of tumor progression and metastasis, to determine effective combinations of therapy with FAK inhibition in the treatment of Ewing sarcoma, and to determine which integrins are necessary for growth, transformation, and FAK activation in Ewing sarcoma.