The Tobacco and Environmental Carcinogenesis Program, which received ?Outstanding? merit in its first CCSG submission in 2010, assembles researchers committed to elucidating how exposures to tobacco and environmental carcinogens cause cancer and how these exposures can be mitigated by risk reduction, intervention, and communication strategies. Exposure to carcinogens represents a major cause of human cancers yet individuals who have the same exposures do not all get cancer in the end-organ. This suggests that significant inter-individual differences exist in cancer susceptibility. Understanding the basis of these differences can lead to precision risk reduction, which represents the translational impact of the Program. The foci of the Program is tobacco related cancers (e.g., lung) and asbestos exposure and mesothelioma, with a developing effort in UV/light exposure and melanoma. Each area provides rich opportunities for inter- Programmatic research. The Program owes its translational and transdisciplinary vision to Co-Leaders Drs. Robert Schnoll, a leader in tobacco control, and Trevor Penning, an expert in environmental carcinogenesis. The scientific aims of the Program are to: 1) Elucidate the pathways underlying exposure risk (e.g., risk factors for tobacco dependence; environmental exposures and risk for mesothelioma and melanoma); 2) Identify the mechanisms linking exposure to disease (e.g., steps in multi-stage carcinogenesis); 3) Evaluate methods for exposure and risk reduction (e.g., tobacco cessation treatments; asbestos remediation; UV light protection); and 4) Test methods of risk communication (e.g., tobacco marketing, regulatory science). Program members collaborate extensively, particularly with the Cancer Control and Cancer Therapeutics Programs, on studies of tobacco use, health communication, and smoking cessation, with the Cancer Therapeutics and Immunobiology Programs on investigations in thoracic oncology and immunotherapies, and with the Melanoma and Cutaneous Malignancies Program on UV/light issues. Seminal contributions during the project period include validating the first genetically-informed biomarker for personalized smoking cessation treatment and identifying novel mechanisms by which multi-organ carcinogens (e.g., polycyclic aromatic hydrocarbons) in tobacco smoke and the environment are metabolically activated. The intra- and inter-Programmatic environment is facilitated by active mentoring, symposia, working groups, and pilot grants. The 15 members, who are from five departments and two schools, have $5.9M in external funding (annual direct costs); $5.8M is peer-reviewed and $2.6M is NCI-funded. Collaborative grants include an NCI P50 Tobacco Center of Regulatory Science (with Cancer Control), a P30 Center of Excellence in Environmental Toxicology (CEET; with Cancer Control), a Pharmacogenomics Research Network U01 (with Cancer Control), and an NIH P42 Superfund Research Program on asbestos. Members authored 263 cancer-related publications (21% intra-Programmatic; 30% inter-Programmatic; 46% multi-institutional) during the project period.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Center Core Grants (P30)
Project #
5P30CA016520-41
Application #
9359401
Study Section
Subcommittee I - Transistion to Independence (NCI)
Program Officer
Marino, Michael A
Project Start
Project End
Budget Start
2016-12-01
Budget End
2017-11-30
Support Year
41
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Type
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
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Yam, Clinton; Xu, Xiaowei; Davies, Michael A et al. (2018) A Multicenter Phase I Study Evaluating Dual PI3K and BRAF Inhibition with PX-866 and Vemurafenib in Patients with Advanced BRAF V600-Mutant Solid Tumors. Clin Cancer Res 24:22-32
Onorati, Angelique V; Dyczynski, Matheus; Ojha, Rani et al. (2018) Targeting autophagy in cancer. Cancer 124:3307-3318
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 :
Garfall, Alfred L; Stadtmauer, Edward A; Hwang, Wei-Ting et al. (2018) Anti-CD19 CAR T cells with high-dose melphalan and autologous stem cell transplantation for refractory multiple myeloma. JCI Insight 3:
Jang, Jeong Hoon; Manatunga, Amita K; Taylor, Andrew T et al. (2018) Overall indices for assessing agreement among multiple raters. Stat Med 37:4200-4215
Scheel, John R; Kim, Eunhee; Partridge, Savannah C et al. (2018) MRI, Clinical Examination, and Mammography for Preoperative Assessment of Residual Disease and Pathologic Complete Response After Neoadjuvant Chemotherapy for Breast Cancer: ACRIN 6657 Trial. AJR Am J Roentgenol 210:1376-1385
Romero, Sally A D; Brown, Justin C; Bauml, Joshua M et al. (2018) Barriers to physical activity: a study of academic and community cancer survivors with pain. J Cancer Surviv 12:744-752
Hinderer, Christian; Katz, Nathan; Buza, Elizabeth L et al. (2018) Severe Toxicity in Nonhuman Primates and Piglets Following High-Dose Intravenous Administration of an Adeno-Associated Virus Vector Expressing Human SMN. Hum Gene Ther 29:285-298
Li, Jinyang; Byrne, Katelyn T; Yan, Fangxue et al. (2018) Tumor Cell-Intrinsic Factors Underlie Heterogeneity of Immune Cell Infiltration and Response to Immunotherapy. Immunity 49:178-193.e7

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