This $414,781 Project Grant awarded by the National Cancer Institute (CFDA 93.395 - Cancer Treatment Research) will support research to investigate the effects of pelvic radiotherapy on the urinary microbiome and its potential as a biomarker for radiation cystitis in prostate cancer patients. The primary awardee, the University of Rochester, will use banked urine samples from a clinical study, as well as a preclinical mouse model, to test hypotheses that: 1) radiotherapy alters the microbial...
The federal Project Grant award R01CA297752 was provided by the National Cancer Institute (NCI) under the Cancer Treatment Research program (CFDA 93.395). The $662,096 grant will fund a 5-year study by the Beckman Research Institute of the City of Hope to characterize the biology driving the response of locally advanced rectal cancer (LARC) to standard of care total neoadjuvant therapy (TNT) with radiation therapy (RT) and chemotherapy. The research aims to determine if intervention with a...
This Project Grant award from the National Cancer Institute (CFDA 93.395 - Cancer Treatment Research) provides $219,024.00 to The University of Texas Health Science Center at Tyler to test the ability of the CSP7 peptide to inhibit radiation-induced lung injury (RILI) and resolve radiation-induced pulmonary fibrosis (RIPF) in mouse models. The award aims to develop a novel peptide intervention for cancer patients undergoing thoracic radiation therapy, which can lead to acute and chronic lung...
The National Cancer Institute awarded a $1,542,555 Project Grant to Sloan-Kettering Institute For Cancer Research under the Cancer Treatment Research program (CFDA 93.395). The grant will fund research from December 2022 through November 2027 to develop more effective treatments for localized bladder cancer. Specifically, the grantee will conduct genomic analyses of bladder cancer patient cohorts to validate DNA damage response mutations as predictors of sensitivity to bacillus Calmette-Guérin...
This federal Project Grant award from the National Cancer Institute (CFDA 93.395 - Cancer Treatment Research) provides $583,973.00 to the Sloan-Kettering Institute for Cancer Research to investigate the role of EP300 mutations in bladder cancer pathogenesis and drug response. The key objectives are to: Study how EP300 loss-of-function mutations mediate resistance to FGFR inhibitors like erdafitinib using patient-derived bladder cancer models. Identify genomic alterations, especially EP300...
This federal Project Grant award of $644,622 from the National Cancer Institute (NCI) under the Cancer Treatment Research program (CFDA 93.395) aims to enhance radioligand therapy for prostate cancer through the development of biomarker and dosimetry-guided personalized treatment approaches. The key objectives are to: 1) develop a novel method for bone marrow dosimetry using macro/micro Monte Carlo modeling, 2) build predictive models to estimate absorbed radiation doses from pre-therapy PET...
This $168,000 Project Grant award from the National Cancer Institute (NCI) under the Cancer Cause and Prevention Research program (CFDA 93.393) supports research to examine risk factors and develop prediction models for multiple recurrences of non-muscle invasive bladder cancer (NMIBC). The primary objectives are to: 1) analyze associations between demographic, lifestyle, social, tumor, comorbidity, and treatment factors and risks of first and multiple NMIBC recurrences, and 2) develop and...
This Project Grant award from the National Institute of Dental and Craniofacial Research (NIDCR), under the Oral Diseases and Disorders Research program (CFDA 93.121), aims to advance understanding of the mechanisms behind radiotherapy resistance in head and neck squamous cell carcinoma (HNSCC). The $320,000 award, effective from July 15, 2025 to July 14, 2027, supports research conducted by Baylor College of Medicine to: Investigate how the KEAP1/NRF2 signaling pathway and the tumor immune...
The National Cancer Institute (NCI), through its Cancer Cause and Prevention Research program (CFDA 93.393), awarded a $1,504,098 Project Grant to the Sloan-Kettering Institute for Cancer Research on May 6, 2025. The grant supports a study to identify genetic determinants of radiation-associated contralateral breast cancer (CBC) and develop a comprehensive integrative model of genetic predisposition to radiation-associated CBC. The research leverages the resources of the WECARE study, a large...
This Project Grant award of $514,582, provided by the National Cancer Institute (CFDA 93.393 - Cancer Cause and Prevention Research) to the University of North Carolina at Chapel Hill, supports research on the role of APOBEC3 enzymes in bladder cancer initiation, progression, and treatment resistance. The research aims to gain a better understanding of how APOBEC3 promotes squamous differentiation in bladder tumors and explore whether co-inhibition of the IL1A pathway can be leveraged to reverse...
THE ROLE OF AMPHIREGULIN IN MEDIATING RADIATION CYSTITIS IN CANCER SURVIVORS - ABSTRACT CANCER SURVIVORS ARE A GROWING POPULATION IN THE UNITED STATES, THOUGH MANY OF THEM PAY A HEAVY PRICE FOR THEIR SURVIVORSHIP STATUS DUE TO LONG-TERM SIDE EFFECTS FROM CANCER THERAPIES. RADIATION CYSTITIS (RC) RESULTS FROM RADIATION THERAPY FOR PELVIC CANCERS. RC IS A DEBILITATING AND PROGRESSIVE BLADDER CONDITION WITH NO EFFECTIVE THERAPY THAT MAY BE LIFE-THREATENING. THUS, THE TREATMENT THAT KILLED THE CANCER, MAY ULTIMATELY KILL THE CANCER SURVIVOR AS WELL. RESEARCH IN CANCER SURVIVORSHIP IS HIGHLY SIGNIFICANT AND REPRESENT A GREAT UNMET NEED. THIS GRANT PROPOSAL IS GREATLY INNOVATIVE AND RESULTS FROM OUR STUDIES MAY LEAD TO NEW DIAGNOSIS AND TREATMENT FOR RADIATION CYSTITIS. THE PI, BERNADETTE ZWAANS, PHD, COMPLETED A SUCCESSFUL AND PRODUCTIVE NIDDK K01 TRAINING AWARD. THE KO1 WAS FOCUSED ON A SYSTEMATIC RESEARCH ON BETTER UNDERSTANDING OF RADIATION CYSTITIS USING SARRP AT THE CAPABLE AND RESOURCEFUL ENVIRONMENT AT BEAUMONT RESEARCH INSTITUTE. WE DEVELOPED AN RC PRECLINICAL MODEL THAT CLOSELY MIMICS THE HUMAN CONDITION. IN THIS MODEL, WE IDENTIFIED THAT RC IS A BIPHASIC CONDITION, CHARACTERIZED BY UROTHELIAL DAMAGE IN THE WEEKS AFTER RADIATION THERAPY (=ACUTE RC), AND BY CHRONIC FIBROSIS, VASCULAR DAMAGE, AND LOSS OF DETRUSOR MUSCLE IN MONTHS TO YEARS AFTER RADIATION THERAPY (= CHRONIC RC). WE HAVE IDENTIFIED AMPHIREGULIN (AREG) TO BE SIGNIFICANTLY ELEVATED AFTER RADIATION THERAPY, AND TO CONTINUE TO GROW IN ABUNDANCE OVER TIME. AREG IS A MEMBER OF THE EPIDERMAL GROWTH FACTOR FAMILY THAT BINDS THE EGF RECEPTOR. IT HAS BEEN IMPLICATED IN MANY PROCESSES INCLUDING TISSUE REGENERATION, CANCER, TISSUE FIBROSIS, AND CELLULAR SENESCENCE. AREG IS PRESENT THROUGHOUT THE BODY BUT IS MOST PROMINENTLY EXPRESSED IN THE BLADDER UROTHELIUM. WE HYPOTHESIZE THAT AREG MEDIATES RADIATION-INDUCED BLADDER FIBROSIS AND CAN SERVE AS A POTENTIAL THERAPEUTIC TARGET. WE FURTHER HYPOTHESIZE THAT AREG CAN SERVE AS A PREDICTIVE URINE BIOMARKER TO IDENTIFY PATIENTS THAT ARE AT RISK FOR DEVELOPING CHRONIC RC. OUR HYPOTHESIS WILL BE TESTED THROUGH THREE SPECIFIC AIMS: 1. DETERMINE THE EXPRESSION PATTERN OF AREG AND ITS IMPORTANCE IN MAINTAINING UROTHELIAL INTEGRITY IN NORMAL AND IRRADIATED BLADDER; 2. DETERMINE THE ROLE OF AREG IN MEDIATING RADIATION-INDUCED FIBROSIS; 3. ASSESS AREG AS A PREDICTIVE BIOMARKER FOR RC. GIVEN OUR EXPERIENCE WITH RC PRECLINICAL MODELS OUR TEAM IS WELL-SUITED TO SUCCESSFULLY COMPLETE THESE AIMS. THIS STUDY IS INVESTIGATING THE FIRST POTENTIAL THERAPEUTIC TARGET FOR RC AND ITS USE AS A PREDICTIVE URINE BIOMARKER. THE OUTCOMES OF OUR STUDIES CAN SIGNIFICANTLY IMPROVE THE QUALITY OF LIFE OF MANY CANCER SURVIVORS SUFFERING FROM SEVERE BLADDER COMPLICATIONS DUE TO RADIATION THERAPY. THUS, THIS STUDY FALLS WITHIN THE MISSION STATEMENT OF THE NIDDK TO IMPROVE HEALTH AND QUALITY OF LIFE OF CANCER SURVIVORS.