Head and neck squamous cell carcinomas (HNSCC) are aggressive neoplasms that result in debilitating changes in speech, appearance, and quality of life in humans. Response rates in HNSCC patients have remained relatively unchanged over the years, especially in patients with human papillomavirus (HPV) negative HNSCC highlighting the critical need for novel strategies to meet the therapeutic needs of this patient population. As recognized by PAR-17-245, a critical step in discovering novel therapies for HNSCC patients is the development of tumor models that can reliably recapitulate human disease biology, heterogeneity and therapeutic response. The overall goal of this application is to validate and credential a panel of patient- derived and immunocompetent models of HNSCC. Systematic and in-depth comparison of histopathologic, genomic, and therapeutic response profiles will be performed across multiple preclinical platforms in vitro (organoids) and in vivo (allografts/xenografts). Paired in vitro and in vivo models across these platforms will be used to assess their response to standard of care chemoradiation and immune checkpoint blockade. The models will also be used to screen the activity of novel and FDA-approved agents (?drug repurposing?) targeting critical pathways implicated in the pathogenesis of HNSCC. The application builds on an existing collaboration between several investigators at Roswell Park Comprehensive Cancer Center with extensive experience and expertise in mammalian models, head and neck cancer, cancer imaging, tumor immunology, genomics, bioinformatics and cancer therapeutics. The project will employ innovative multimodal functional imaging methods to better define and enhance the true translational utility of mammalian models. The proposal will establish a robust panel of credentialed mammalian models of HNSCC and enable development of an integrated preclinical pipeline to assess efficacy of novel therapeutics, identify resistance mechanisms and enable biomarker discovery in HNSCC.

Public Health Relevance

The overall goal of this application is to enhance the translational applicability of mammalian tumor models by performing a cross-comparative evaluation of in vitro (organoids) and in vivo (xenograft/allograft) models of head and neck cancer. Consistent with the objectives of PAR-17-245, we propose to perform a systematic in- depth comparison of histopathologic, radiologic, genomic, and therapeutic response profiles across these multiple preclinical platforms. In addition to testing standard of care treatment regimens, paired in vitro and in vivo models will be used to screen the activity of novel and FDA-approved agents targeting critical pathways implicated in the pathogenesis of HNSCC.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA243456-01A1
Application #
10136888
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Watson, Joanna M
Project Start
2020-12-01
Project End
2025-11-30
Budget Start
2020-12-01
Budget End
2021-11-30
Support Year
1
Fiscal Year
2021
Total Cost
Indirect Cost
Name
Roswell Park Cancer Institute Corp
Department
Type
DUNS #
824771034
City
Buffalo
State
NY
Country
United States
Zip Code
14263