TUMOR PROGRESSION AND RECURRENCE PROGRAM Project Summary The major goals of the Tumor Progression and Recurrence (TPR) Program are to understand the molecular mechanisms that promote tumor progression and recurrence and use this knowledge to develop novel strategies to treat cancer, particularly those with high rates of recurrence, relentless progression, or high incidence/high mortality in the Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) catchment area. These goals will be achieved by the Program members' research around two central themes: cellular signaling and the tumor microenvironment. The cellular signaling theme reflects a focus on mechanisms that are both important for cancer progression and potential targets for therapeutics. The tumor microenvironment theme focuses on interactions between cancer cells and other cell types within tumors that promote tumor progression and facilitate recurrence. The research of the TPR Program centers particularly on malignant gliomas, including glioblastoma; metastatic breast cancer; and prostate cancer. In all of these, tumor progression and/or recurrence are particularly important. The focus on prostate cancer also reflects its high rates of occurrence in the WFBCCC catchment area, especially among African Americans. The Program has two Specific Aims.
Aim 1 is to determine the signaling pathways and molecular targets in cancer cells and other cell types in the tumor microenvironment that promote tumor progression and recurrence.
Aim 2 is to identify novel therapeutic approaches for difficult-to-treat cancers, based on disrupting signaling between cancer cells and other cells in the tumor microenvironment, and drug delivery targeted to cells in the tumor microenvironment. Examples include targeting interactions of Ephrin ligands and their Eph receptors and delivery of cytotoxic load, development of peptides that target the Mas receptor, and development of oncolytic viruses that target defects in antiviral signaling in cancers. New members recruited into the Program since the last review further strengthen the research portfolio around the two Program themes. The Program has 31 members from 14 different departments or sections, including Biochemistry, Biomedical Engineering, Cancer Biology, Comparative Medicine, Human Genomics, Microbiology and Immunology, Molecular Medicine, Neurosurgery, Pathology, Radiation Oncology, Radiology, Regenerative Medicine, and Surgery. Program members have $4.4M in extramural peer-reviewed funding (excluding $.7M in peer-reviewed training grants), of which 37.2% is from the NCI. Among the members' 247 publications, 23.5% were intra-programmatic, 17.0% were inter-programmatic, and 66.4% were inter-institutional, demonstrating the collaborative spirit and national and international stature of the Program's research.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Center Core Grants (P30)
Project #
2P30CA012197-42
Application #
9209694
Study Section
Special Emphasis Panel (NCI (K1)-A)
Project Start
Project End
Budget Start
2017-02-01
Budget End
2018-01-31
Support Year
42
Fiscal Year
2017
Total Cost
$45,195
Indirect Cost
$16,037
Name
Wake Forest University Health Sciences
Department
Type
Domestic Higher Education
DUNS #
937727907
City
Winston-Salem
State
NC
Country
United States
Zip Code
27157
Feliz-Mosquea, Yismeilin R; Christensen, Ashley A; Wilson, Adam S et al. (2018) Combination of anthracyclines and anti-CD47 therapy inhibit invasive breast cancer growth while preventing cardiac toxicity by regulation of autophagy. Breast Cancer Res Treat 172:69-82
Holmila, Reetta J; Vance, Stephen A; Chen, Xiaofei et al. (2018) Mitochondria-targeted Probes for Imaging Protein Sulfenylation. Sci Rep 8:6635
Rego, Stephen L; Harvey, Scott; Simpson, Sean R et al. (2018) TREX1 D18N mice fail to process erythroblast DNA resulting in inflammation and dysfunctional erythropoiesis. Autoimmunity :1-12
Li, X C; Wang, M Y; Yang, M et al. (2018) A mutational signature associated with alcohol consumption and prognostically significantly mutated driver genes in esophageal squamous cell carcinoma. Ann Oncol 29:938-944
Lu, Yong; Wang, Qiang; Xue, Gang et al. (2018) Th9 Cells Represent a Unique Subset of CD4+ T Cells Endowed with the Ability to Eradicate Advanced Tumors. Cancer Cell 33:1048-1060.e7
Godwin, Ryan C; Macnamara, Lindsay M; Alexander, Rebecca W et al. (2018) Structure and Dynamics of tRNAMet Containing Core Substitutions. ACS Omega 3:10668-10678
Peak, Taylor C; Praharaj, Prakash P; Panigrahi, Gati K et al. (2018) Exosomes secreted by placental stem cells selectively inhibit growth of aggressive prostate cancer cells. Biochem Biophys Res Commun 499:1004-1010
Akter, Salma; Fu, Ling; Jung, Youngeun et al. (2018) Chemical proteomics reveals new targets of cysteine sulfinic acid reductase. Nat Chem Biol 14:995-1004
Han, Fei; Li, Chien-Feng; Cai, Zhen et al. (2018) The critical role of AMPK in driving Akt activation under stress, tumorigenesis and drug resistance. Nat Commun 9:4728
Chmielewski, Jeffrey P; Bowlby, Sarah C; Wheeler, Frances B et al. (2018) CD38 Inhibits Prostate Cancer Metabolism and Proliferation by Reducing Cellular NAD+ Pools. Mol Cancer Res 16:1687-1700

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