Search Prime Grants

P01CA275740

Project Grant

Overview

Grant Description
Exploiting therapeutic vulnerabilities in hepatocellular carcinoma (ELEVATE) - Overall: Summary

Hepatocellular carcinoma (HCC), the primary malignancy of hepatocytes, is a diagnosis with bleak outcomes.

With the alarming rise in global obesity incidence, obesity-induced non-alcoholic steatohepatitis (NASH) is becoming a leading cause of HCC.

HCC is usually diagnosed at an advanced stage when the tumor is unresectable.

The most effective FDA-approved treatment for advanced non-resectable HCC is a combination of anti-PD-L1 (atezolizumab) and anti-VEGF (bevacizumab) antibodies, providing an overall response rate of 27%.

Apart from immunotherapy, systemic therapy with tyrosine kinase inhibitors (TKIs, such as sorafenib or lenvatinib) provides only a modest (~3 months) increase in overall survival and causes drug resistance within six months.

Recent studies document that immunotherapy may be less effective in patients with NASH-HCC than in HCC patients with viral hepatitis.

Thus, there is an unmet need to develop novel and effective modalities of treatment for advanced HCC.

This P01 proposal exploiting therapeutic vulnerabilities in hepatocellular carcinoma (ELEVATE), which involves four projects, an administrative core (Core 1), a mouse model and pathological analysis core (Core 2), and a biostatistics and bioinformatics core (Core 3; BBC), aims to interrogate molecular changes in HCC and exploit them to develop combinatorial treatment approaches especially targeted to NASH-HCC.

The overall objectives include interrogation of molecular mechanisms regulating NASH-HCC and the development of novel combinatorial treatment approaches based on the identified molecular abnormalities, evaluation of approaches that improve efficacy of approved immunotherapy using an authentic NASH-HCC mouse model, and development and evaluation of novel approaches that engage the immune system to counteract HCC (inflammatory and NASH-HCC).

To achieve this objective, this P01 comprises experts, with an established history of highly integrated interaction, in HCC biology and mouse modeling, liver physiology and pathology, medicinal chemistry, cancer immunotherapy, pathological diagnosis, nanoparticle delivery, and bioinformatics and biostatistics.

Successful completion of the proposed studies will significantly advance our understanding of the molecular mechanism of HCC pathogenesis and novel therapeutics and generate translationally relevant data from pre-clinical models having the potential to radically transform the management of HCC patients facilitating prolonged survival.

Thus, this innovative P01 grant has high mechanistic and translational significance.

ELEVATE brings together the expertise of a highly integrated team providing synergistic outcomes that may not be delivered by each project alone.
Funding Goals
TO DEVELOP THE MEANS TO CURE AS MANY CANCER PATIENTS AS POSSIBLE AND TO CONTROL THE DISEASE IN THOSE PATIENTS WHO ARE NOT CURED. CANCER TREATMENT RESEARCH INCLUDES THE DEVELOPMENT AND EVALUATION OF IMPROVED METHODS OF CANCER TREATMENT THROUGH THE SUPPORT AND PERFORMANCE OF BOTH FUNDAMENTAL AND APPLIED LABORATORY AND CLINICAL RESEARCH. RESEARCH IS SUPPORTED IN THE DISCOVERY, DEVELOPMENT, AND CLINICAL TESTING OF ALL MODES OF THERAPY INCLUDING: SURGERY, RADIOTHERAPY, CHEMOTHERAPY, AND BIOLOGICAL THERAPY INCLUDING MOLECULARLY TARGETED THERAPIES, BOTH INDIVIDUALLY AND IN COMBINATION. IN ADDITION, RESEARCH IS CARRIED OUT IN AREAS OF NUTRITIONAL SUPPORT, STEM CELL AND BONE MARROW TRANSPLANTATION, IMAGE GUIDED THERAPIES AND STUDIES TO REDUCE TOXICITY OF CYTOTOXIC THERAPIES, AND OTHER METHODS OF SUPPORTIVE CARE THAT MAY SUPPLEMENT AND ENHANCE PRIMARY TREATMENT. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO EXPAND AND IMPROVE THE SBIR PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.
Grant Program (CFDA)
Place of Performance
Richmond, Virginia 232985017 United States
Geographic Scope
Single Zip Code
Analysis Notes
Amendment Since initial award the total obligations have increased 99% from $2,678,459 to $5,325,147.
Virginia Commonwealth University was awarded ELEVATE : Novel Therapeutic Approaches Hepatocellular Carcinoma Project Grant P01CA275740 worth $5,325,147 from National Cancer Institute in August 2024 with work to be completed primarily in Richmond Virginia United States. The grant has a duration of 5 years and was awarded through assistance program 93.395 Cancer Treatment Research. The Project Grant was awarded through grant opportunity National Cancer Institute Program Project Applications for the Years 2023, 2024, and 2025 (P01 Clinical Trial Optional).

Status
(Ongoing)

Last Modified 8/20/25

Period of Performance
8/8/24
Start Date
7/31/29
End Date
21.0% Complete

Funding Split
$5.3M
Federal Obligation
$0.0
Non-Federal Obligation
$5.3M
Total Obligated
100.0% Federal Funding
0.0% Non-Federal Funding

Activity Timeline

Interactive chart of timeline of amendments to P01CA275740

Transaction History

Modifications to P01CA275740

Additional Detail

Award ID FAIN
P01CA275740
SAI Number
P01CA275740-2423104589
Award ID URI
SAI UNAVAILABLE
Awardee Classifications
Public/State Controlled Institution Of Higher Education
Awarding Office
75NC00 NIH National Cancer Institute
Funding Office
75NC00 NIH National Cancer Institute
Awardee UEI
MLQFL4JSSAA9
Awardee CAGE
46050
Performance District
VA-04
Senators
Mark Warner
Timothy Kaine
Modified: 8/20/25