Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Targeting Adaptive Radioresistance of Glioblastoma

Award Number: K22CA263305
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 01/01/2023
PERIOD OF PERFORMANCE END DATE: 12/31/2025

Group Awards By:

View Award Description

Targeting Adaptive Radioresistance of Glioblastoma - PROJECT SUMMARY Glioblastoma (GBM) is a lethal brain cancer treated by surgery, radiotherapy, and chemotherapy. While fractionated radiation therapy (60Gy delivered over 4-6 weeks) is efficacious in killing many cancer cells, a subset gains radioresistance and survive, leading to tumor recurrence. Understanding the mechanisms underlying adaptive radioresistance may lead to new therapeutic approaches to overcome radioresistance. To decipher radioresistance mechanisms, we need sophisticated models that reflect the genetic heterogeneity of GBM, including the stem cell population, which is considered to be particularly prone to acquiring radioresistance. Till now, only limited radioresistance models have been developed and the role of glioma stem cells (GSCs) has not been properly examined. To address this gap in knowledge, I developed novel preclinical models of mouse and human GSCs that were progressively adapted to repeated irradiation. Using these models, I identified a novel resistance mechanism driven by IGF1-induced N-cadherin signaling validating my approach. To identify additional radioresistance genes, I performed a genome-wide CRISPR library screening in radioresistant human GSCs and found new candidate genes, including Syndecan 1 (SDC1). I showed that SDC1 expression is increased in 4 different radioresistant GSC lines and correlates with malignancy and poor outcome of patients with malignant glioma (TCGA database). Knockout of SDC1 in radioresistant GSCs restored radio-sensitivity, decreased IGF1R expression and suppressed IGF1R signaling. As prior literature has shown that SDC1 and IGF1R interact, these findings suggest that SDC1 and IGF1R might be components of the same radioresistance pathway. Based on this rationale, I hypothesize that increased SDC1 expression induces adaptive GBM radioresistance by activating IGF1R signaling; and that blocking SDC1-induced IGF1R activation will antagonize radioresistance and increase survival. I will test my hypothesis through the following aims: 1) examine how SDC1 confers GSC radioresistance, 2) determine how SDC1 activates IGF1R signaling, and 3) evaluate the efficacy of targeting SDC1-induced radioresistance in mouse models. My project is innovative because the role of SDC1- IGF1R-mediated signaling in GSC radioresistance has never been examined. This project will lead to the development of future my research and will become a foundation for my future career. My career plan is to systematically identify the drivers and related signaling mechanisms underlying radioresistance in GSCs. I have a dual background as a neurosurgeon and basic neuro-oncology researcher and have further secured the support of advisors and professional collaborators (see letters of support). Successful completion of this project will lead to the development of better therapies for the treatment of therapy-resistant GBM and propel my transition to an independent investigator in neuro-oncology.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $0 )
2026	2025	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Cancer Research Manpower	000	3	5/4/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $108,000 )
2025	2025	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Cancer Research Manpower	000	3	12/4/2024	NON-COMPETING CONTINUATION	$108,000
														Subtotal = $108,000

Issue Date FY: 2024 ( Subtotal = $108,000 )
2024	2024	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Cancer Research Manpower	000	2	1/19/2024	NON-COMPETING CONTINUATION	$108,000
														Subtotal = $108,000

Issue Date FY: 2023 ( Subtotal = $108,000 )
2023	2023	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Cancer Research Manpower	000	1	11/23/2022	NEW	$108,000
														Subtotal = $108,000

Grand Total All Awards = $324,000

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Targeting Adaptive Radioresistance of Glioblastoma

Award Number: K22CA263305

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 01/01/2023

PERIOD OF PERFORMANCE END DATE: 12/31/2025

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer