The Tumor Development Program focuses on understanding the genetic, epigenetic and developmental processes that take place in tumor-initiating cells and tumor-susceptible tissues during tumor development. The Program was established in 2007 by combining the Oncodevelopmental Biology Program with the Cancer Genetics &Epigenetics Program. This merger logically combines expertise in developmental aspects of cancer with genetic and epigenetic mechanisms underiying cancer development. Drs. Robert Oshima and Manuel Perucho are co-Leaders of the Program, which consists of 14 full members and 2 adjunct members. The Program comprises three overarching themes, which benefit from highly interdisciplinary program membership, including expertise in genetic and epigenetic pathways, stem cell biology, mouse models of cancer and medicinal chemistry: 1- Genetic and epigenetic changes in cancer. Program members continue to lead the field of the """"""""mutator phenotype"""""""" and carcinogenesis, with additional strengths in the areas of chromatin modifications, cell cycle regulation and checkpoint signaling, and RNA biology;2- Stem cell biology, with focus of Notch and Wnt signaling, and mouse models of cancer, with focus on mammary gland and colon models. The Program is a resource for all CCSG Programs due to its expertise in mouse tumor models;and 3- Novel targets in cancer treatment, with focus on nuclear receptors and retinoic acids. Notably, members of the Program have developed a retinoid-like drug, Targretin?, which is FDA-approved for the treatment cutaneous T cell lymphoma. Members of this collaborative and multidisciplinary Program interact at a number of levels, including monthly faculty meetings and through collaborative grants. Program funding is currently at $12.9MM in annual total costs ($7.0MM direct). Program members participate in two POIs (1 from NCI), three U54/U19 grants, and 15 additional collaborative peer-reviewed federal and state grants. Program members also have 17 NIH ROIs (7 from NCI). The Program's productivity is further reflected by 345 publications since last review, and by 58 Program publications in 2008, which represent 14% of intra- and 21% of inter-programmatic collaborations, respectively.

Public Health Relevance

The Tumor Development Program tackles the fundamental causes underlying tumor inifiafion and development. Understanding the eariy genefic, epigenefic and developmental changes and defects that occur in tumor-initiating cells and tumor-susceptible tissues is expected to lead into novel therapies that target eariy stages of cancer, or key cell populations that continue to drive malignancy of late stage tumors.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Center Core Grants (P30)
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Subcommittee G - Education (NCI)
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Sanford-Burnham Medical Research Institute
La Jolla
United States
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Barile, Elisa; Marconi, Guya D; De, Surya K et al. (2017) hBfl-1/hNOXA Interaction Studies Provide New Insights on the Role of Bfl-1 in Cancer Cell Resistance and for the Design of Novel Anticancer Agents. ACS Chem Biol 12:444-455
Attali, Ilan; Tobelaim, William Sam; Persaud, Avinash et al. (2017) Ubiquitylation-dependent oligomerization regulates activity of Nedd4 ligases. EMBO J 36:425-440
Linares, Juan F; Cordes, Thekla; Duran, Angeles et al. (2017) ATF4-Induced Metabolic Reprograming Is a Synthetic Vulnerability of the p62-Deficient Tumor Stroma. Cell Metab 26:817-829.e6
Todoric, Jelena; Antonucci, Laura; Di Caro, Giuseppe et al. (2017) Stress-Activated NRF2-MDM2 Cascade Controls Neoplastic Progression in Pancreas. Cancer Cell 32:824-839.e8
Scortegagna, Marzia; Berthon, Annabel; Settas, Nikolaos et al. (2017) The E3 ubiquitin ligase Siah1 regulates adrenal gland organization and aldosterone secretion. JCI Insight 2:
Jellusova, Julia; Cato, Matthew H; Apgar, John R et al. (2017) Gsk3 is a metabolic checkpoint regulator in B cells. Nat Immunol 18:303-312
Avellaneda Matteo, Diego; Grunseth, Adam J; Gonzalez, Eric R et al. (2017) Molecular mechanisms of isocitrate dehydrogenase 1 (IDH1) mutations identified in tumors: The role of size and hydrophobicity at residue 132 on catalytic efficiency. J Biol Chem 292:7971-7983
Lee, Bongyong; Sahoo, Anupama; Marchica, John et al. (2017) The long noncoding RNA SPRIGHTLY acts as an intranuclear organizing hub for pre-mRNA molecules. Sci Adv 3:e1602505
McKeithan, Wesley L; Savchenko, Alex; Yu, Michael S et al. (2017) An Automated Platform for Assessment of Congenital and Drug-Induced Arrhythmia with hiPSC-Derived Cardiomyocytes. Front Physiol 8:766
Toome, Kadri; Willmore, Anne-Mari A; Paiste, Päärn et al. (2017) Ratiometric in vivo auditioning of targeted silver nanoparticles. Nanoscale 9:10094-10100

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