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Non-invasive characterization of human soft tissue sarcoma response to radiation therapy

人类软组织肉瘤对放射治疗反应的非侵入性表征

基本信息

批准号：
10448722
负责人：
Everett James Moding
金额：
$ 26.22万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-08-15 至 2026-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10448722
关键词：
Adjuvant Adjuvant Therapy Adult Aftercare Architecture Biological Markers Biology Blood specimen Cancer Biology Cancer Personalized Profiling by Deep Sequencing Cell Line Cells Clinical Research Clinical Trials Combined Modality Therapy Computational Biology DNA analysis Data Disease Distant Metastasis Doctor of Philosophy Enrollment External Beam Radiation Therapy Foundations Future Gene Expression Genetic Genetic Determinism Genomics Goals Histologic Human Hybrids Immunotherapy K-Series Research Career Programs Knowledge Laboratories Lead Localized Disease Malignant Neoplasms Mediating Mediator of activation protein Medicine Mentors Mentorship Mesenchymal Mesenchymal Cell Neoplasm Modeling Modernization Molecular Monitor Mus Mutation Operative Surgical Procedures Outcome Patient-Focused Outcomes Patients Pattern Phase II Clinical Trials Physicians Plasma Pre-Clinical Model Primary Neoplasm Probability Radiation Oncology Radiation Tolerance Radiation therapy Radiobiology Radiosurgery Randomized Recurrence Relapse Research Research Proposals Residual Tumors Risk Factors Role Sampling Scientist Soft tissue sarcoma Systemic Therapy Systems Biology Techniques Testing Training Treatment-related toxicity Tumor Tissue Universities Validation Work base design experimental study high risk improved improved outcome individual patient insight medical schools mouse model new combination therapies novel patient response peripheral blood personalized medicine pre-clinical predicting response professor prognostic model programs prospective radiation resistance radiation response radioresistant randomized trial relapse prediction relapse risk response sarcoma symposium therapy development therapy resistant tool transcriptomics translational research program tumor tumor DNA tumor eradication tumor immunology tumor microenvironment

项目摘要

PROJECT SUMMARY/ABSTRACT Everett Moding, MD, PhD is an Assistant Professor of Radiation Oncology at Stanford University School of Medicine. His long-term goal is to use his combined expertise in clinical and research medicine to make important discoveries in radiation and cancer biology that lead to better treatments for patients with sarcomas. He hopes to develop a translational research program using analysis of human tumor and blood samples to identify critical mediators of radiation resistance that can be validated in preclinical models and leveraged to enhance the efficacy of radiation therapy. The goal of this career development award is to provide support and mentorship to enable Dr. Moding to develop a successful independent research program. The proposal will be carried out under the mentorship of physician scientists Maximilian Diehn, MD, PhD, an expert in genomicsbased biomarkers, Ash Alizadeh, MD, PhD, an expert in tumor immunology and transcriptomic analysis tools, and David Kirsch, MD, PhD, a leader in radiation biology and mouse models. The training plan incorporates formal coursework, seminars, conferences, and programs along with informal hands-on and practical activities to expand Dr. Moding’s knowledge and expertise in 1) computational and systems biology, 2) tumor immunology and sarcoma biology, and 3) laboratory management, mentoring, and grantsmanship. Soft tissue sarcomas (STS) are a diverse group of mesenchymal tumors primarily managed with surgery and radiation therapy for localized disease. Although half of patients with high risk STS develop metastatic disease after initial therapy, there are no biomarkers to identify patients at risk of relapse. In addition, up to two-thirds of patients with STS develop local recurrences after radiation therapy alone, but the underlying genetic alterations that mediate radiation resistance are unknown. By analyzing tumor and peripheral blood samples collected from 102 patients enrolled on the SU2C-SARC032 phase II clinical trial, this research proposal aims to 1) establish personalized circulating tumor DNA analysis as a biomarker in patients with STS, 2) build a prognostic model integrating tumor microenvironment profiling, circulating tumor DNA analysis, and traditional risk factors to improve prediction of patient outcomes, and 3) use circulating tumor DNA analysis and tumor sequencing to identify genetic alterations that mediate the response of sarcomas to radiation therapy for rapid functional validation in novel preclinical platforms. This proposal will lay the groundwork for future prospective randomized trials using circulating tumor DNA analysis and tumor genomics to enable personalized treatment approaches in patients with STSs that improve the probability of tumor eradication while minimizing treatment-related toxicity.

项目总结/文摘