Stress is a fundamental part of life for all cells and organisms and dealing successfully with stress facilitates survival in cells and whole organisms. Oncogenic transformation creates substantial intrinsic cell stress (e.g. metabolic, proteotoxic, DNA damage stresses). Tumor cells respond to intrinsic stress in numerous, highly conserved ways, some of which facilitate cell survival. Tumor growth may also cause changes in the microenvironment in which malignant cells develop - changes which add additional extrinsic stress factors (e.g. inflammation, hypoxia, high interstitial fluid pressure, nutritional deprivation, low pH). Finally, anticancer therapy adds to both intrinsic cell stress and may change the tumor microenvironment, modifying those stress factors, too. Cell Stress and Biophysical Therapies (CSBT) Program members are committed to understanding the mechanisms and responses in tumor cells which help them evade anticancer therapies as well as host antitumor responses. The overall goal of the CSBT Program is to identify, understand and exploit tumor cell stress and microenvironment mechanisms, and to use this to develop novel therapies. Members share interest in the imaging and therapy potential for modalities such as light, heat and ionizing radiation energies. There are three research themes in the program and each integrates basic, translational and clinical science: 1) Understanding intrinsic cancer cell stress mechanisms, 2) Understanding stress mechanisms in the host/tumor microenvironment and 3) Protecting normal cells/tissues from therapy-induced damage. The Program is co-led by Drs. Andrei Gudkov and Elizabeth Repasky each of whom has successful and complimentary research programs that span the themes of the program. Retreats and monthly program meetings focus on basic and translational research and discussions of new collaborations and clinical trial opportunities. Since the last review, the laboratories of the CSBT members have moved into closer proximity in the newly constructed Center for Genetics and Pharmacology. The program is comprised of 20 members from 8 different RPCI departments. Current annual total peer-reviewed program funding is $S.4M, of which $2.6M is NCI, and the total extramural research funding is $6.9M. Of the 353 publications of CSBT members over the last funding cycle, 21% are intra-programmatic and 20% are inter-programmatic. Importantly, the number of high impact papers (Impact Factor>10) has significantly increased (10 to 33) while at the same time, the major goal of developing new clinical trials emerging from research developed within the CSBT Program continues to be very strong and successful.

Public Health Relevance

It is now clear that the stress response in tumors, combined with stress-induced damage to normal tissues, are significant factors in therapeutic failure and tumor regrowth/metastasis. A more complete understanding of the mechanisms whereby stress, and stress responses increase the resistance of tumor cells to death, while exposing normal tissues to significant damage, will enable identification of new factors to target for blocking the responses and will increase tumor sensitivity to therapy.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Center Core Grants (P30)
Project #
2P30CA016056-37
Application #
8738360
Study Section
Subcommittee G - Education (NCI)
Project Start
1997-06-16
Project End
2019-04-30
Budget Start
2014-06-26
Budget End
2015-04-30
Support Year
37
Fiscal Year
2014
Total Cost
$37,715
Indirect Cost
$14,918
Name
Roswell Park Cancer Institute Corp
Department
Type
DUNS #
824771034
City
Buffalo
State
NY
Country
United States
Zip Code
14263
Zhao, Zhiguo; Wen, Wanqing; Michailidou, Kyriaki et al. (2016) Association of genetic susceptibility variants for type 2 diabetes with breast cancer risk in women of European ancestry. Cancer Causes Control 27:679-93
Goossens, Maria E; Isa, Fatima; Brinkman, Maree et al. (2016) International pooled study on diet and bladder cancer: the bladder cancer, epidemiology and nutritional determinants (BLEND) study: design and baseline characteristics. Arch Public Health 74:30
Clyde, Merlise A; Palmieri Weber, Rachel; Iversen, Edwin S et al. (2016) Risk Prediction for Epithelial Ovarian Cancer in 11 United States-Based Case-Control Studies: Incorporation of Epidemiologic Risk Factors and 17 Confirmed Genetic Loci. Am J Epidemiol 184:579-589
Wilton, John; Kurenova, Elena; Pitzonka, Laura et al. (2016) Pharmacokinetic analysis of the FAK scaffold inhibitor C4 in dogs. Eur J Drug Metab Pharmacokinet 41:55-67
Sexton, Sandra; Tulowitzki, Ryan; Jones, Craig A et al. (2016) Involvement of the renin-angiotensin system in the development of nephrogenic systemic fibrosis-like lesions in the RenTag mouse model. Clin Exp Nephrol 20:162-8
Shafirstein, Gal; Battoo, Athar; Harris, Kassem et al. (2016) Photodynamic Therapy of Non-Small Cell Lung Cancer. Narrative Review and Future Directions. Ann Am Thorac Soc 13:265-75
Pharoah, Paul D P; Song, Honglin; Dicks, Ed et al. (2016) PPM1D Mosaic Truncating Variants in Ovarian Cancer Cases May Be Treatment-Related Somatic Mutations. J Natl Cancer Inst 108:
Austin, David C; Strand, Douglas W; Love, Harold L et al. (2016) NF-κB and androgen receptor variant 7 induce expression of SRD5A isoforms and confer 5ARI resistance. Prostate 76:1004-18
Rohrbach, Daniel J; Rigual, Nestor; Arshad, Hassan et al. (2016) Intraoperative optical assessment of photodynamic therapy response of superficial oral squamous cell carcinoma. J Biomed Opt 21:18002
Chinnam, Meenalakshmi; Wang, Xiaoling; Zhang, Xiaojing et al. (2016) Evaluating Effects of Hypomorphic Thoc1 Alleles on Embryonic Development in Rb1 Null Mice. Mol Cell Biol 36:1621-7

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