Targeting the epigenetic and metabolic control of EBV-epithelial cancers - overall

Active Project Grant Awarded Last action

Award ID
P01CA269043
Recipient
Awarding agency
Obligated
$14,277,597

Award facts

Assistance listing
93.396 Cancer Biology Research
Completion date 70% complete
Place of performance
Philadelphia, PA 19104, USA

Award details come from USAspending.gov.

Description

Abstract
The overall aim of this new program project (P01) proposal is to generate highly collaborative and integrated basic and translational research on the urgent, unmet medical need of epithelial cancers caused by epstein-barr virus (EBV). EBV latent infection is causally linked to over 200,000 new cancer cases per year. EBV epithelial cancers represent over 75% of all EBV cancers with highest mortality rates and treatment failures. EBV- associated gastric carcinoma (EBVAGC) and nasopharyngeal carcinoma (NPC) have many similarities with respect to viral latency and oncogenic transformation. The mechanisms through which EBV contributes to these epithelial cancers remains elusive, and to date, there are no viral-specific therapies that are FDA approved to treat cancers infected with EBV. We have assembled a team of EBV investigators with expertise in complementary aspects of tumor virology and cancer biology, with specific areas of interest in viral genetics, epigenetics, metabolism, drug discovery, and models of EBV carcinogenesis. The program team will collaborate in a coordinated strategy to identify key viral and cellular vulnerabilities in EBV epithelial cancers that can be targeted for therapeutic intervention. The program will test the central hypothesis that EBV cancers arise in the context of somatic mutations in metabolic and epigenetic pathways that alter EBV latency and oncogenicity, and how this viral-host CO-dependency provides therapeutic opportunities. To achieve these goals for the program we propose three projects and three scientific cores to address the following: (1) determine how EBV establishes a latent and oncogenic infection in epithelial cancer cells (2) determine how EBV latent infection drives epigenetic and metabolic shifts including the formation of CPG island methylator phenotype (CIMP) to promote epithelial cell oncogenesis. (3) leverage mechanistic insights to develop new therapeutic strategies to treat EBV epithelial cancers. The 3 projects focus broadly on EBV latency and epigenome (LIEBERMAN), parp, NAD and DNA damage metabolism (TEMPERA), and DNA methylation and methionine metabolism (GEWURZ). The 3 scientific cores support bioinformatics, drug discovery, and models of EBV cancers to support each of the 3 projects as research enhancers. Together, this team and program will investigate key features of EBV cancer mechanisms, build new tools to study EBV cancers, and develop new therapeutic strategies that are viral-specific and precision-based medicine.

Transactions

Action Obligated Date
Amendment $2,411,466
Amendment $2,420,381
Amendment $2,286,821
Amendment $2,286,821
Amendment $2,436,054
Original award $2,436,054

Subawards

Subrecipient Amount Awarded
Brigham & Womens Physician Organization, Inc. Dr. Gewurz will be responsible for the direction and experimental plan for the studies in Aim 3. Dr. Gewurz will work closely with Drs. Lieberman, Tempera and… $1,845,553
Brigham & Womens Physician Organization, Inc. $908,896

Quick answers

Who received award P01CA269043?

P01CA269043 was awarded to The Wistar Institute Of Anatomy And Biology by National Cancer Institute (National Institutes of Health) on May 11, 2023.

How much is award P01CA269043 worth?

$14,277,597 has been obligated on P01CA269043.

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