The Free Radical Cancer Biology Program (FRCBP) is unique to the HCCC and focuses on studying the biology of inherent differences in reductive and oxidative (redox) metabolism between cancer vs. normal cells. Research in the program is determining the role that redox reactions play in cancer phenotypic changes relevant to cell growth, differentiation, signal transduction, metastasis, functional molecular imaging, and therapy. A unifying goal of the program is to utilize a comprehensive basic science understanding of redox biology to develop novel biochemical rationales for improving cancer therapy. Three overlapping themes exist within the program. Theme 1: Understanding the role of redox biochemistry in regulation of genetic and epigenetic gene expression pathways relevant to cancer biology. Within this theme are research areas of focus exploring redox fluctuations and gene expression globally, as well as gene expression changes related of key redox sensitive molecules such as glutathione, thioredoxin, SOD, and AP2. Ttieme 2: Understanding the role of redox regulation in cell biology. Within this theme are research areas exploring the effects of redox on the cell cycle as well as invasion and metastasis. Ttieme 3: Exploring the role of oxidative stress in therapy outcomes. Within this theme are research areas exploring the role of manipulating oxidative stress to improve therapy as well as using imaging of oxidative metabolism as an approach to monitor and guide therapy. Major accomplishments of the FRCBP over the past funding period include findings that (a) cancer cells (relative to normal cells) produce increased steady-state levels of 02*'and H2O2 from mitochondrial metabolism that significantly contribute to differential susceptibility to clonogenic cell killing induced by glucose deprivation;(b) extracellular superoxide dismutase (EcSOD) inhibits invasion and metastasis;(c) expression of MnSOD governs the late production of reactive oxygen species, cell cycle check points, and transformation following radiation exposure;(d) that inhibitors of glucose and hydroperoxide metabolism can be used to enhance responses to radio-chemo-therapy by enhancing metabolic oxidative stress. The FRCBP consists of 18 members from 1 basic science department and 6 clinical departments and 2 colleges. Peer-reviewed, research funding for this program totals $3.9 million with over $2.0 million total costs from NCI. FRCBP members co-authored 237 publications. Of these publications, 20% were intraprogrammatic, 24% were interprogrammatic and 10% were both intra and interprogrammatic, for a total of 54% collaborative publications.

Public Health Relevance

It is becoming clear that metabolic oxidation/reduction reactions are altered in cancer vs. normal cells. The consensus is that cancer cells may exist in a chronic state of metabolic oxidative stress that may represent a significant underlying mechanism contributing to malignancy. A unifying goal of research in the FRCBP is to utilize a comprehensive understanding of cancer vs. normal cell redox biology to develop novel biochemical rationales for improving cancer therapy taking advantage fundamental differences in oxidative metabolism.

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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University of Iowa
Iowa City
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Chrisman, Matthew; Nothwehr, Faryle; Janz, Kathleen et al. (2015) Perceived Resources and Environmental Correlates of Domain-Specific Physical Activity in Rural Midwestern Adults. J Phys Act Health 12:962-7
Chrisman, Matthew; Nothwehr, Faryle; Yang, Ginger et al. (2015) Environmental influences on physical activity in rural Midwestern adults: a qualitative approach. Health Promot Pract 16:142-8
Makkouk, Amani; Weiner, George J (2015) Cancer immunotherapy and breaking immune tolerance: new approaches to an old challenge. Cancer Res 75:10-May
Naderi, Ali (2015) Coagulation factor VII is regulated by androgen receptor in breast cancer. Exp Cell Res 331:239-50
McDowell, Bradley D; Chapman, Cole G; Smith, Brian J et al. (2015) Pancreatectomy predicts improved survival for pancreatic adenocarcinoma: results of an instrumental variable analysis. Ann Surg 261:740-5
Ponto, Laura L Boles; Menda, Yusuf; Magnotta, Vincent A et al. (2015) Frontal hypometabolism in elderly breast cancer survivors determined by [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET): a pilot study. Int J Geriatr Psychiatry 30:587-94
Chrischilles, Elizabeth A; McDowell, Bradley D; Rubenstein, Linda et al. (2015) Survivorship care planning and its influence on long-term patient-reported outcomes among colorectal and lung cancer survivors: the CanCORS disease-free survivor follow-up study. J Cancer Surviv 9:269-78
Makkouk, Amani; Joshi, Vijaya B; Wongrakpanich, Amaraporn et al. (2015) Biodegradable microparticles loaded with doxorubicin and CpG ODN for in situ immunization against cancer. AAPS J 17:184-93
Bhama, A R; Charlton, M E; Schmitt, M B et al. (2015) Factors associated with conversion from laparoscopic to open colectomy using the National Surgical Quality Improvement Program (NSQIP) database. Colorectal Dis 17:257-64
Hoover, Andrew C; Milhem, Mohammed M; Anderson, Carryn M et al. (2015) Efficacy of nelfinavir as monotherapy in refractory adenoid cystic carcinoma: Results of a phase II clinical trial. Head Neck 37:722-6

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