U01CA263957

NCI Pediatric In Vivo Testing Program: Neuroblastoma - Project Summary

Children with disseminated neuroblastoma have a very high risk of treatment failure and death despite receiving intensified chemotherapy, radiation therapy, and immunotherapy. The long-term goal of the Mosse and Maris translational research programs is to substantively improve neuroblastoma cure rates by developing patient-specific therapies that target the unique oncogenic drivers of each case.

Within the context of the National Cancer Institute's Pediatric In Vivo Testing Program (PED-IN VIVO-TP), we propose a neuroblastoma research program built on richly annotated and highly characterized patient-derived xenograft (PDX) and other recently developed murine models of this disease. The central hypothesis to be tested in this program is that neuroblastoma-specific oncogenic drivers and optimal immunotherapeutic targets can be defined and exploited through rationally designed therapies based on validated and clinically measurable biomarkers.

Through our dedicated focus on neuroblastoma and our central role in the former Pediatric Preclinical Testing Program and Consortium, we have developed an investigative team and rich set of resources and reagents to be uniquely positioned to achieve the goals of the PED-IN VIVO-TP. Here, we propose to use a large (and growing) collection of PDX models that have been fully characterized with the most modern genomic technologies to address the challenge of prioritizing the large armamentarium of anti-cancer agents in development. This will enable us to design early phase biomarker-driven clinical trials with the objective of showing potent and specific anti-tumor activity.

We propose three specific aims directed towards:
1) Developing and characterizing highly annotated models of human neuroblastoma;
2) Performing preclinical trials with drugs directed against defined therapeutic vulnerabilities in order to prioritize agents for the clinic; and
3) Developing the portfolio of preclinical data required for the design of clinical trials with robust biomarkers for patient selection and monitoring.

In collaboration with other preclinical testing programs, we will seek to determine if discoveries in our program are relevant to other childhood cancers and collaborate across disease groups on clinical development strategies. Thus, this program will seek to shift the paradigm for how high-risk neuroblastoma patients are treated with the goal of substantively improving the outcomes, both in terms of cure rates, but also by decreasing the toxicity associated with current standards of care.

The Children's Hospital Of Philadelphia

TO DEVELOP THE MEANS TO CURE AS MANY CANCER PATIENTS AS POSSIBLE AND TO CONTROL THE DISEASE IN THOSE PATIENTS WHO ARE NOT CURED. CANCER TREATMENT RESEARCH INCLUDES THE DEVELOPMENT AND EVALUATION OF IMPROVED METHODS OF CANCER TREATMENT THROUGH THE SUPPORT AND PERFORMANCE OF BOTH FUNDAMENTAL AND APPLIED LABORATORY AND CLINICAL RESEARCH. RESEARCH IS SUPPORTED IN THE DISCOVERY, DEVELOPMENT, AND CLINICAL TESTING OF ALL MODES OF THERAPY INCLUDING: SURGERY, RADIOTHERAPY, CHEMOTHERAPY, AND BIOLOGICAL THERAPY INCLUDING MOLECULARLY TARGETED THERAPIES, BOTH INDIVIDUALLY AND IN COMBINATION. IN ADDITION, RESEARCH IS CARRIED OUT IN AREAS OF NUTRITIONAL SUPPORT, STEM CELL AND BONE MARROW TRANSPLANTATION, IMAGE GUIDED THERAPIES AND STUDIES TO REDUCE TOXICITY OF CYTOTOXIC THERAPIES, AND OTHER METHODS OF SUPPORTIVE CARE THAT MAY SUPPLEMENT AND ENHANCE PRIMARY TREATMENT. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO EXPAND AND IMPROVE THE SBIR PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.395 - Cancer Treatment Research

National Cancer Institute (NCI) [HHS - NIH]

Philadelphia, Pennsylvania 191043820 United States

Single Zip Code

NCI Pediatric In Vivo Testing Program (U01 Clinical Trial Not Allowed) (RFA-CA-20-034)

Amendment Since initial award the total obligations have increased 398% from $712,800 to $3,549,742.