DF/HCC Members Awarded New or Competitively Renewed Federal Funding
The NIH continues to recognize DF/HCC as a leader in cancer research by awarding several new multi-investigator grants to DF/HCC members.
The proposed research will develop novel methods to assess mediation and interaction between genetic and environmental exposures and different disease subtypes so as to better tailor treatments and prevention efforts to individuals' characteristics and so as to better understand the mechanisms governing disease. Methods will be developed for settings in which there are multiple disease subtypes and these disease subtypes may have different prognosis for survival and may be more amenable to different types of treatment and preventive efforts. Methodology for assessing the role of interaction in understanding mechanisms will also be developed. This will include elucidating the role of gene-environment interaction in the heritability of disease, understanding mediating pathways from exposure to disease in the presence of interaction, and identifying sufficient cause interaction for diseases or disease subtypes such that an outcome would occur if two (or more) exposures are present, but not if only one or the other were present.
We propose to study the determinants of NAD+ metabolism in IDH mutant gliomas. Our application is relevant to the public health because IDH mutant gliomas are diagnosed in young adults, ages 20-50 years old, and there are no effective systemic therapies when surgery and radiation fail to offer durable disease control for these cancers. Relevant to the NCI mission, the objective of this study is to understand changes that are associated with sensitivity to specific metabolite perturbation, to inform strategies that can improve the efficacy of novel targeted therapies, with the goal to identify optimal therapeutic approaches for this disease.
The Metabolic Pathogenesis of Chromophobe Renal Cell Carcinoma
NIA - 1R01CA216922-01A1
PI: Elizabeth Henske (BWH), Carmen Priolo (BWH)
Our long-term goal is to determine the fundamental metabolic mechanisms contributing to chromophobe renal cell carcinoma (ChRCC) tumorigenesis. The fundamental mechanisms of ChRCC pathogenesis remain a key knowledge gap. We aim to identify paradigm-shifting targeted therapeutic opportunities for patients with recurrent or metastatic ChRCC, for whom there are currently no proven therapeutic options. The clinical impact of this project would be identifying such novel therapeutic strategies for ChRCC.
Implementing A Virtual Tobacco Treatment in Community Oncology Practices
NCI - 1R01CA214427-01A1
PIs: Elyse Park (MGH), Jamie Ostroff (MSKCC)
We propose to conduct an effectiveness-implementation trial to assess virtual delivery of an evidence-based tobacco treatment intervention in cancer community sites affiliated with the newly established ECOG-ACRIN NCI Community Oncology Research Program. This study has the potential to close the gap of evidence-based tobacco treatment delivery in resource sparse community oncology settings.
Comprehensive Characterization of Prostate Stromal Gene Expression and Associate With Lethal Prostate Cancer
NCI - 1R01CA227190-01
PIs: Kathryn Penney (BWH), Svilana Tyekucheva (DFCI)
The pressing need to distinguish potentially lethal from indolent prostate cancer is usually approached by attempting to identify genomic predictors in the malignant epithelial tissue. However, from extensive cell biology research, it is known that the microenvironment plays a critical role in cancer progression, though a deeper understanding of the mechanism is needed. In this proposal, we will study gene expression of the prostate microenvironment to improve the understanding of its impact on the biology of the tumor and to augment previously proposed genomic predictors of lethal prostate cancer by developing a gene expression signature from the stromal tissue.
Directed Purinergic Signaling as Immunotherapy in Leukemia
NCI - 1R21CA221702-01A1
PIs: Simon Robson (BIDMC), David Avigan (BIDMC)
We will test whether innovative anti-CD39 reagents re-purpose purinergic signaling to correct the immunosuppressive tumor microenvironment seen in acute myeloid leukemia. Modification of anti-CD39 will be attempted to cause depletion of T regulatory cells to further elicit potent tumor rejection. At the conclusion of this work, we will have identified optimal therapeutic anti-CD39 regimens to boost purinergic immune responses in leukemia that could be immediately translated and tested in clinical studies.
Integrating Diet and Tissue Whole Exome Sequencing Data to Study Processed Meat and Colorectal Cancer
NCI - 1R21CA222940-01
PIs: Kana Wu (HSPH), Reiko Nishihara (BWH)
Even though processed meat is an established risk factor for colorectal cancers, underlying mechanisms remain unknown. This timely proposal will shed more light into hypothesized and possibly novel pathways and consequently inform dietary guidelines for cancer prevention and guide food reformulation efforts to minimize processed meat toxicity.