The intent of the Wistar/Penn SPORE in Skin Cancer is to decrease the morbidity and mortality of skin cancers through improved understanding of the pathogenesis of these diseases using novel, validated molecular biomarkers of risk, progression and prognosis and the development of targeted therapies. This SPORE is focused on major skin cancers: melanoma, cutaneous T cell lymphoma (CTCL) and squamous cell carcinoma (SCC). The overall goals of this SPORE are to address five translationally important areas: 1) Risk assessment. We will test the hypothesis that susceptibility to melanoma stems from complex interactions of multiple factors, including inherited genotypes, environmental exposures, and endogenous pigmentation (Projects 1 and 2). 2) Risk prediction. Genotypes (Projects 1 and 2) will be integrated with existing risk factors to develop prediction models of individual melanoma risk. These models will be important in stratifying individuals for screening and prevention, and to enhance the efficacy of targeted prevention trials. 3) Prognosis. Using data from Projects 1 (alterations in DNA), and 2 and 3 (differences in protein levels) we will develop and externally validate comprehensive, biologically based prognostic models that will be used in clinical trials and in patient management. 4) Diagnosis. We will develop and validate biomarkers to distinguish melanoma in situ from invasive and/or tumorigenic melanoma (Project 3). 5) Therapy. We will investigate several novel therapies for advanced melanoma and CTCL (Projects 4, 5 and 6). These include: a) targeted therapy for melanoma: molecular targeting of MAP kinase signaling pathways capitalizing on the recent discovery that the majority of human melanomas have an activating mutation in BRAF (Project 6); b) cytokine therapy of CTCL: determination of the mechanisms whereby CTCL becomes refractory to recombinant human IL-12-based therapies and how therapeutic efficacy can be enhanced by cytokines, including IL-2 (Project 5); and c) active and passive immunotherapy of melanoma with lymphocytes and defined tumor antigens: an organotypic model of melanoma will define new cytotoxic T-cell specificities against human melanoma, leading to the identification of novel antigens for vaccine trials and """"""""optimized"""""""" adoptive immunotherapy (Project 4). The Wistar/Penn SPORE addresses the most aggressive cancers of the skin. It is focused on melanoma because of its rising incidence and significant potential for lethality. It is the subject of five of the six Projects and three of the five Pilot Studies. CTCL is addressed in one Project and one Pilot Study, and SCC in one Pilot Study. This endeavor represents the synergistic integration of well-established individual research programs towards our collective goals.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
3P50CA093372-06S1
Application #
7495242
Study Section
Special Emphasis Panel (ZCA1-GRB-V (O1))
Program Officer
Ogunbiyi, Peter
Project Start
2001-09-28
Project End
2009-06-30
Budget Start
2007-08-14
Budget End
2008-06-30
Support Year
6
Fiscal Year
2007
Total Cost
$96,729
Indirect Cost
Name
Wistar Institute
Department
Type
DUNS #
075524595
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Ojha, Rani; Leli, Nektaria M; Onorati, Angelique et al. (2018) ER translocation of the MAPK pathway drives therapy resistance in BRAF mutant melanoma. Cancer Discov :
Kugel 3rd, Curtis H; Douglass, Stephen M; Webster, Marie R et al. (2018) Age Correlates with Response to Anti-PD1, Reflecting Age-Related Differences in Intratumoral Effector and Regulatory T-Cell Populations. Clin Cancer Res 24:5347-5356
Nti, Akosua A; Serrano, Leona W; Sandhu, Harpal S et al. (2018) FREQUENT SUBCLINICAL MACULAR CHANGES IN COMBINED BRAF/MEK INHIBITION WITH HIGH-DOSE HYDROXYCHLOROQUINE AS TREATMENT FOR ADVANCED METASTATIC BRAF MUTANT MELANOMA: Preliminary Results From a Phase I/II Clinical Treatment Trial. Retina :
Onorati, Angelique V; Dyczynski, Matheus; Ojha, Rani et al. (2018) Targeting autophagy in cancer. Cancer 124:3307-3318
Noguera-Ortega, Estela; Amaravadi, Ravi K (2018) Autophagy in the Tumor or in the Host: Which Plays a Greater Supportive Role? Cancer Discov 8:266-268
Rebecca, Vito W; Nicastri, Michael C; Fennelly, Colin et al. (2018) PPT1 promotes tumor growth and is the molecular target of chloroquine derivatives in cancer. Cancer Discov :
Garman, Bradley; Anastopoulos, Ioannis N; Krepler, Clemens et al. (2017) Genetic and Genomic Characterization of 462 Melanoma Patient-Derived Xenografts, Tumor Biopsies, and Cell Lines. Cell Rep 21:1936-1952
Rebecca, Vito W; Nicastri, Michael C; McLaughlin, Noel et al. (2017) A Unified Approach to Targeting the Lysosome's Degradative and Growth Signaling Roles. Cancer Discov 7:1266-1283
Ndoye, Abibatou; Budina-Kolomets, Anna; Kugel 3rd, Curtis H et al. (2017) ATG5 Mediates a Positive Feedback Loop between Wnt Signaling and Autophagy in Melanoma. Cancer Res 77:5873-5885
Taylor, Laura A; Abraham, Ronnie M; Tahirovic, Emin et al. (2017) High ALDH1 expression correlates with better prognosis in tumorigenic malignant melanoma. Mod Pathol 30:634-639

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