# ExpLoiting thErapeutic VulnerAbilities in hepaTocEllular carcinoma (ELEVATE)

> **NIH NIH P01** · VIRGINIA COMMONWEALTH UNIVERSITY · 2024 · $2,678,459

## Abstract

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 theErapeutic 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.

## Key facts

- **NIH application ID:** 10849086
- **Project number:** 1P01CA275740-01A1
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **Principal Investigator:** Devanand Sarkar
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $2,678,459
- **Award type:** 1
- **Project period:** 2024-08-08 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10849086

## Citation

> US National Institutes of Health, RePORTER application 10849086, ExpLoiting thErapeutic VulnerAbilities in hepaTocEllular carcinoma (ELEVATE) (1P01CA275740-01A1). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10849086. Licensed CC0.

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