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Mentored Career Development Award: Isothiocyanates to Improve Response to Proton Radiotherapy

指导职业发展奖：异硫氰酸盐改善质子放射治疗的反应

基本信息

批准号：
10705559
负责人：
Christina A Wicker
金额：
$ 10万
依托单位：
UNIVERSITY OF CINCINNATI
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：
2022-09-16 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10705559
关键词：
Apoptotic Award Biological Assay Cancer Biology Cancer Patient Cancerous Cell Death Cell Death Signaling Process Cell Line Cell Survival Cells Cisplatin Clinical Trials Clinical Trials Design Comet Assay Committee Members DNA Damage Data Dental Down-Regulation Drug Targeting Functional disorder Future Gene Expression Regulation Generations Genes Genetic Transcription Goals Head and Neck Cancer Head and Neck Squamous Cell Carcinoma Head and neck structure Health Hematology Human Immunology Induction of Apoptosis Isothiocyanates K-Series Research Career Programs Knowledge Malignant Neoplasms Mediating Mentored Research Scientist Development Award Mentors Mentorship Mission Modeling Morbidity - disease rate National Institute of Dental and Craniofacial Research Neoplasm Metastasis Normal Cell Normal tissue morphology Oncology Oral Oral health Organoids Outcome Oxidative Stress Oxidative Stress Induction Pain Pathway interactions Patient-Focused Outcomes Patients Phenethyl Isothiocyanate Photons Phytochemical Proton Radiation Protons Radiation Radiation Oncology Radiation Protection Radiation therapy Radiobiology Radiosensitization Reactive Oxygen Species Research Research Personnel Research Proposals Resistance Resources Signal Pathway Testing Therapeutic Training Transcription Alteration Treatment Efficacy Ulcer United States National Institutes of Health Up-Regulation Validation Western Blotting alternative treatment cancer cell cancer therapy cancer type career development craniofacial cytokine dietary antioxidant dietary supplements disadvantaged background efficacy evaluation head and neck cancer patient improved improved outcome in vivo in vivo evaluation innovation insight interest keratinocyte mortality multidisciplinary neoplastic cell novel novel strategies novel therapeutic intervention pre-clinical preservation pro-apoptotic protein radiation effect radiation resistance radiation response radioprotected research and development response side effect standard of care success therapy resistant transcriptome sequencing transcriptomics treatment and outcome treatment response treatment strategy tumor tumor growth

项目摘要

Project Summary/Abstract This application is for a Mentored Career Development Award to Promote Diversity in the Dental, Oral and Craniofacial Research Workforce (K01). I am testing the hypothesis that combining a dietary antioxidant with proton radiation will improve outcome in patients with head and neck cancer (HNC). This award will provide me with the resources I need to achieve the following goals: (1) To become a leading expert in proton radiation as well as novel therapeutic strategies to improve outcome in patients with HNC. (2) To complete the research and career development activities proposed in this application. (3) To increase the visibility of, to mentor and to promote inclusion of researchers who are underrepresented or who are from a disadvantaged background in the field of HNC. To achieve these goals, I have assembled a multidisciplinary mentorship team with complementary expertise. These include: (1) Dr. Vinita Takiar (primary mentor, radiation oncology and HNC), (2) Dr. Susan Waltz (co-primary mentor, tumor growth, senior researcher, microenvironment and metastasis), (3) Dr. Trisha Wise-Draper (committee member, hematology oncology, immunology and HNC), (4) Dr. Susanne Wells (committee member, senior researcher, organoids, proton and photon radiation, and HNC). Resistance to therapeutic treatment in head and neck squamous cell carcinoma (HNSCC), a form of HNC, significantly contributes to increased morbidity and mortality. As salvage options remain limited, there is a critical need to develop novel therapeutic approaches to extend survival in patients with HNSCC. Previous research by the PI and others has demonstrated that the dietary antioxidant isothiocyanate compounds can sensitize cancer cells to radiation and cytokine. Isothiocyanates also protect normal cells from the effects of radiation. The long-term goal of this project is to improve patient outcomes by improving treatment response. The overall objective of this proposal is to test whether isothiocyanate, phenethyl isothiocyanate (PEITC), in combination with proton radiation, generates increased DNA damage and lethality in HNSCC cells. The central hypothesis is that the combination of proton radiation with PEITC is superior to the current standard of care combination, which is cisplatin with photon beam therapy (XRT). To examine the central hypothesis, we propose the following specific aims: 1) Examine how PEITC enhances proton radiation mediated cell death and 2) investigate the effects of PEITC in protecting normal head and neck cells from radiation. Developing alternative treatment strategies to improve radiation response is significant since failed response to radiation results in decreased patient survival. This research proposal is innovative in that it focuses on utilizing well- tolerated, dietary antioxidants as an alternative strategy to overcoming radiation resistance in HNSCC and employs the use of cutting edge proton radiation. This proposal will ultimately provide insight and mechanistic understanding into developing alternative treatment strategies to overcome radiation treatment resistance in HNSCC patients as well as potentially other cancer types.

项目总结/文摘