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The University of Texas MD Anderson Cancer Center SPORE in Melanoma

德克萨斯大学 MD 安德森癌症中心 SPORE 黑色素瘤

基本信息

批准号：
10415934
负责人：
Michael Davies
金额：
$ 205.87万
依托单位：
UNIVERSITY OF TX MD ANDERSON CAN CTR
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-07-16 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10415934
关键词：
Address Adjuvant Adoptive Cell Transfers Adult Affinity Bioinformatics Biometry Carrier Proteins Cause of Death Cessation of life Clinical Clinical Research Clinical Trials Common Neoplasm Communication Community Health Cutaneous Melanoma Cytotoxic T-Lymphocytes Data Analyses Development Disease Distant Metastasis Ensure Epitopes Eye Neoplasms Faculty Funding Future Genomics Goals Immune Immune checkpoint inhibitor Immune response Immunologics Immunology Immunotherapeutic agent Immunotherapy In complete remission Incidence Investigation Knowledge Lead Left Malignant Neoplasms Mentors Metastatic Melanoma Metastatic Neoplasm to the Central Nervous System Molecular Molecular Biology Neuraxis Nivolumab Non-Cutaneous Melanoma Outcome PD-1 blockade PTEN gene Pathogenesis Pathology Pathway interactions Patients Pilot Projects Population Refractory Research Research Personnel Resistance Resources Safety Service provision Services Site Skin Cancer Survival Rate Testing Therapeutic Toxic effect Translating Translational Research Treatment Failure University of Texas M D Anderson Cancer Center Uveal Melanoma anti-PD-1 anti-PD1 antibodies anti-PD1 therapy burden of illness career clinical database clinical investigation combinatorial data sharing design effective therapy experience experimental study global health immunogenic improved insight meetings melanoma microbiome mortality multidisciplinary novel novel strategies novel therapeutic intervention novel therapeutics patient subsets programmed cell death protein 1 programs research study resistance mechanism response targeted treatment therapy resistant tissue resource treatment site treatment strategy tumor

项目摘要

Overall: Project Summary/Abstract Melanoma is the deadliest form of skin cancer, with an increasing incidence and mortality, and a 5-year survival rate less than 20% for patients with metastatic disease. Several recent landmark genomic and immunologic studies have generated important new insights into the pathogenesis, drivers, and regulators of this disease, translating into the approval of both targeted and immune therapies for patients with metastatic disease. While targeted therapies have achieved high response rates, they are generally transient; likewise, immunotherapies bring about dramatic, long-term, complete responses but only in a subset of patients and often with serious toxicities. Despite the progress that has been made, several key challenges remain to maximizing the clinical benefit of immunotherapy: 1) poorly understood markers and mechanisms of resistance to immunotherapy, and a lack of effective strategies to overcome them; 2) limited experience or efficacy in patients with central nervous system involvement, a common metastatic site and cause of death for melanoma and other cancers; and 3) lack of any benefit from single-agent immunotherapies in patients with non-cutaneous melanomas, particularly the uveal melanoma subtype. The central hypothesis of this SPORE proposal is that an integrated analysis of immune and molecular features in patients with advanced melanoma will improve our understanding of response and resistance to immunotherapy, and lead to more effective treatments. To test this hypothesis, we will focus on the most critical unmet needs of melanoma patients, building on current immunotherapeutic strategies and developing our own novel concepts to identify more effective treatment options by pursuing the following specific aims: • Address resistance to the PD-1 immune checkpoint inhibitor through inhibition of the PI3K pathway in PTEN- null metastatic melanoma patients (Project 1). • Determine the clinical utility of PD-1 blockade using nivolumab administered intrathecally in metastatic melanoma patients with leptomeningeal disease (Project 2). • Evaluate a new therapeutic strategy for uveal melanoma that uses adoptive cell therapy to target an immunogenic epitope of melanosomal transport protein SLC45A2 (Project 3). Three cores (Administrative Core, Clinical Database, Tissue Resource, and Translational Pathology Core [Core 2] and Biostatistics and Bioinformatics Core [Core 3]) provide specialized services to support our SPORE investigators and their proposed research studies. Together, these three projects and cores and our Developmental Research and Career Enhancement Programs will provide a comprehensive attack on critical unmet needs for patients battling these deadly manifestations of melanoma, and pave the way for other cancers with limited therapeutic options.

总体：项目摘要/摘要