Monday, June 30, 2025 6/30/2025

Personalizing immunotherapy in HER2+ breast cancer through quantitative imaging

Award Number: R01CA240589
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/01/2020
PERIOD OF PERFORMANCE END DATE: 02/28/2025

Group Awards By:

View Award Description

Personalizing immunotherapy in HER2+ breast cancer through quantitative imaging - PROJECT SUMMARY/ABSTRACT The overall goal of this proposal is to integrate advanced imaging and mathematical modeling to optimize combination treatments involving immunotherapy in human epidermal growth factor receptor type 2 positive (HER2+) breast cancer. Current standard-of-care therapeutic regimens and even clinical trials are limited because they are not personalized based on the tumor biology of the individual patient, potentially diminishing the efficacy of the treatment. This proposed research will employ noninvasive, quantitative magnetic resonance imaging (MRI) and positron emission tomography (PET) to inform mathematical models to direct timing for multi-modal therapies in HER2+ breast cancer. Overexpression of HER2 is indicative of more aggressive disease with five times higher risk of metastasis, with increased risk of breast-to-brain metastases, compared to HER2- patients. We have extensive experience and expertise in using quantitative medical imaging techniques to assess and predict treatment response to anti-cancer therapies. Additionally, we have shown that trastuzumab dosing prior to cytotoxic treatment (instead of simultaneous dosing of combination therapies) has potential to improve vascular delivery and oxygenation in HER2+ breast cancer tumors, which in turns sensitizes the tumor for cytotoxic therapies, reduces metastatic potential, improves drug delivery and reduces systemic toxicity. As immunotherapy becomes mainstream for many solid tumors, it is essential to develop techniques to both personalize and optimize therapeutic efficacy and decrease systemic toxicity. Thus, our central hypothesis is that quantitative imaging integrated with mathematical modeling can enhance personalization of treatment strategies and increase efficacy (additive and synergistic) of combination therapies with immunotherapy in HER2+ breast cancer. To achieve this goal, we have identified the following specific aims: 1) Quantify biological changes to immuno- and targeted therapy in HER2+ breast cancer with quantitative imaging, 2) Build a mathematical model of biological alterations to immunotherapy in HER2+ breast cancer, and 3) Employ model forecasting and quantitative imaging to guide combination therapy. We will exploit the alterations in biological changes, such as vascular delivery (evaluated with dynamic contrast enhanced (DCE)- MRI pharmacokinetic parameter, Ktrans) and oxygenation (evaluated with fluoromisonidazole (FMISO)-PET imaging metric, SUV) to inform a mathematical model in order to identify (and validate) optimal sequencing (order, timing, dose) to combination therapy (targeted, immunotherapy) for enhanced synergistic effects. Completion of this project provides a pathway to dramatically improve the efficacy of treatment strategies with immunotherapy for primary HER2+ breast cancer. Importantly, the proposed techniques provide a straightforward route for patient translation and potential to enhance care for HER2+ breast cancer patients.


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: 2025 ( Subtotal = $0 )
2025	2023	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Cancer Detection and Diagnosis Research	000	4	6/12/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $404,986 )
2023	2023	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Cancer Detection and Diagnosis Research	000	4	2/1/2023	NON-COMPETING CONTINUATION	$404,986
														Subtotal = $404,986

Issue Date FY: 2022 ( Subtotal = $413,866 )
2022	2022	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Cancer Detection and Diagnosis Research	000	3	2/11/2022	NON-COMPETING CONTINUATION	$372,475
2022	2022	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Cancer Detection and Diagnosis Research	001	3	5/25/2022	NON-COMPETING CONTINUATION	$41,391
														Subtotal = $413,866

Issue Date FY: 2021 ( Subtotal = $391,680 )
2021	2021	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Cancer Detection and Diagnosis Research	000	2	2/2/2021	NON-COMPETING CONTINUATION	$391,680
														Subtotal = $391,680

Issue Date FY: 2020 ( Subtotal = $414,223 )
2020	2020	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Cancer Detection and Diagnosis Research	000	1	2/13/2020	NEW	$414,223
														Subtotal = $414,223

Grand Total All Awards = $1,624,755

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Personalizing immunotherapy in HER2+ breast cancer through quantitative imaging

Award Number: R01CA240589

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 03/01/2020

PERIOD OF PERFORMANCE END DATE: 02/28/2025

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer