The National Cancer Institute (NCI) has released a Notice of Funding Opportunity (NOFO) titled "Epidemiologic Research on Emerging Risk Factors and Liver Cancer Susceptibility" (PA-25-123) under the R21 Exploratory/Developmental Research Grant mechanism. This opportunity is reissued from PAR-22-084 and seeks to fund research on emerging biological, environmental, and social risk factors for liver cancer in the U.S., especially their interactions with established risk factors like viral hepatitis. Applicants may also explore rare histological subtypes of liver cancer, including cholangiocarcinoma, hepatoblastoma, and angiosarcoma, contributing to the overall liver cancer burden. This grant will support studies that could expand the knowledge base to inform liver cancer prevention and control strategies and operates alongside a companion R01 opportunity for larger research projects.

The purpose of this NOFO is to address the rising incidence and mortality rates of liver cancer, particularly hepatocellular carcinoma (HCC), in the U.S. Researchers are encouraged to study emerging non-viral factors—such as obesity, diabetes, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and exposure to substances like PFAS—that may contribute to liver cancer. Other focal areas include potential interactions of these factors with viral hepatitis and socio-demographic disparities in liver cancer incidence and progression across different populations. The grant also supports studies investigating novel hypotheses related to liver carcinogenesis, including the influence of the microbiome and various biomarkers.

The maximum direct cost for the two-year project period is capped at $275,000, with no more than $200,000 allowed in any single year. This NOFO does not support clinical trials, and applications must be submitted in compliance with the latest NIH application guidelines, which include updated FORMS-I. Eligible applicants include higher education institutions, nonprofits, for-profits, government agencies, and foreign organizations. Multi-institution collaborations are encouraged, as is the use of existing case-control or cohort studies and databases to test research hypotheses.

To apply, applicants must follow detailed guidelines from NIH’s How to Apply Application Guide. All prospective applicants should ensure registration with System for Award Management (SAM), eRA Commons, and Grants.gov. While letters of intent are not required, they are encouraged to help NCI anticipate review workload. Applications are due on February 16, 2025, with the earliest project start date in December 2025. NIH peer review will evaluate scientific merit based on the research's significance, rigor, feasibility, and investigator expertise, with separate assessments for each category.

Important administrative requirements include mandatory disclosure of federal criminal law violations affecting awards, adherence to NIH data management and sharing policies, and detailed reporting obligations via the Research Performance Progress Report (RPPR) if the award is made. For additional assistance, applicants may contact relevant NIH officials, with designated contacts for application support, scientific questions, biospecimen inquiries, and financial management.