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
Miller, James A; Harris, Kassem; Roche, Charles et al. (2018) Sarcopenia is a predictor of outcomes after lobectomy. J Thorac Dis 10:432-440
Fenstermaker, Robert A; Figel, Sheila A; Qiu, Jingxin et al. (2018) Survivin Monoclonal Antibodies Detect Survivin Cell Surface Expression and Inhibit Tumor Growth In Vivo. Clin Cancer Res 24:2642-2652
Bhat, Tariq A; Kalathil, Suresh Gopi; Bogner, Paul N et al. (2018) Secondhand Smoke Induces Inflammation and Impairs Immunity to Respiratory Infections. J Immunol 200:2927-2940
Merzianu, Mihai; Groman, Adrienne; Hutson, Alan et al. (2018) Trends in Bone Marrow Sampling and Core Biopsy Specimen Adequacy in the United States and Canada: A Multicenter Study. Am J Clin Pathol 150:393-405
Qin, Bo; Llanos, Adana A M; Lin, Yong et al. (2018) Validity of self-reported weight, height, and body mass index among African American breast cancer survivors. J Cancer Surviv 12:460-468
Qiao, Guanxi; Chen, Minhui; Bucsek, Mark J et al. (2018) Adrenergic Signaling: A Targetable Checkpoint Limiting Development of the Antitumor Immune Response. Front Immunol 9:164
Muramatsu, Masashi; Akakura, Shin; Gao, Lingqiu et al. (2018) SSeCKS/Akap12 suppresses metastatic melanoma lung colonization by attenuating Src-mediated pre-metastatic niche crosstalk. Oncotarget 9:33515-33527
Kumar, Sandeep; Inigo, Joseph R; Kumar, Rahul et al. (2018) Nimbolide reduces CD44 positive cell population and induces mitochondrial apoptosis in pancreatic cancer cells. Cancer Lett 413:82-93
Liu, Chunhong; Yu, Tao; Xing, Zhuo et al. (2018) Triplications of human chromosome 21 orthologous regions in mice result in expansion of megakaryocyte-erythroid progenitors and reduction of granulocyte-macrophage progenitors. Oncotarget 9:4773-4786
Cimato, Thomas R; Conway, Alexis; Nichols, Julianne et al. (2018) CD133 expression in circulating hematopoietic progenitor cells. Cytometry B Clin Cytom :

Showing the most recent 10 out of 1555 publications