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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Gong, Xiao-Min; Ding, Yi; Yu, Jinghua et al. (2015) Structure of the Na,K-ATPase regulatory protein FXYD2b in micelles: implications for membrane-water interfacial arginines. Biochim Biophys Acta 1848:299-306
Brun, S N; Markant, S L; Esparza, L A et al. (2015) Survivin as a therapeutic target in Sonic hedgehog-driven medulloblastoma. Oncogene 34:3770-9
You, Weon-Kyoo; Yotsumoto, Fusanori; Sakimura, Kenji et al. (2014) NG2 proteoglycan promotes tumor vascularization via integrin-dependent effects on pericyte function. Angiogenesis 17:61-76
Vargas, Lina M; Leal, Nancy; Estrada, Lisbell D et al. (2014) EphA4 activation of c-Abl mediates synaptic loss and LTP blockade caused by amyloid-? oligomers. PLoS One 9:e92309
Volkmann, Niels; Page, Christopher; Li, Rong et al. (2014) Three-dimensional reconstructions of actin filaments capped by Arp2/3 complex. Eur J Cell Biol 93:179-83
Bailey, Ann M; Zhan, Le; Maru, Dipen et al. (2014) FXR silencing in human colon cancer by DNA methylation and KRAS signaling. Am J Physiol Gastrointest Liver Physiol 306:G48-58
Valencia, Tania; Kim, Ji Young; Abu-Baker, Shadi et al. (2014) Metabolic reprogramming of stromal fibroblasts through p62-mTORC1 signaling promotes inflammation and tumorigenesis. Cancer Cell 26:121-35
Northcott, Paul A; Lee, Catherine; Zichner, Thomas et al. (2014) Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma. Nature 511:428-34
Kim, H; Claps, G; Moller, A et al. (2014) Siah2 regulates tight junction integrity and cell polarity through control of ASPP2 stability. Oncogene 33:2004-10
Finlay, Darren; Vamos, Mitchell; Gonzalez-Lopez, Marcos et al. (2014) Small-molecule IAP antagonists sensitize cancer cells to TRAIL-induced apoptosis: roles of XIAP and cIAPs. Mol Cancer Ther 13:5-15

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