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
Ciamporcero, Eric; Miles, Kiersten Marie; Adelaiye, Remi et al. (2015) Combination strategy targeting VEGF and HGF/c-met in human renal cell carcinoma models. Mol Cancer Ther 14:101-10
Ma, Yingyu; Hu, Qiang; Luo, Wei et al. (2015) 1?,25(OH)2D3 differentially regulates miRNA expression in human bladder cancer cells. J Steroid Biochem Mol Biol 148:166-71
Shen, Li; Sundstedt, Anette; Ciesielski, Michael et al. (2015) Tasquinimod modulates suppressive myeloid cells and enhances cancer immunotherapies in murine models. Cancer Immunol Res 3:136-48
Adelaiye, Remi; Ciamporcero, Eric; Miles, Kiersten Marie et al. (2015) Sunitinib dose escalation overcomes transient resistance in clear cell renal cell carcinoma and is associated with epigenetic modifications. Mol Cancer Ther 14:513-22
Uekusa, Shota; Kawashima, Hiroyuki; Sugito, Kiminobu et al. (2014) Nr4a3, a possibile oncogenic factor for neuroblastoma associated with CpGi methylation within the third exon. Int J Oncol 44:1669-77
Ambrosone, Christine B; Zirpoli, Gary; Ruszczyk, Melanie et al. (2014) Parity and breastfeeding among African-American women: differential effects on breast cancer risk by estrogen receptor status in the Women's Circle of Health Study. Cancer Causes Control 25:259-65
Röhm, Marc; Grimm, Melissa J; D'Auria, Anthony C et al. (2014) NADPH oxidase promotes neutrophil extracellular trap formation in pulmonary aspergillosis. Infect Immun 82:1766-77
Rohrbach, Daniel J; Muffoletto, Daniel; Huihui, Jonathan et al. (2014) Preoperative mapping of nonmelanoma skin cancer using spatial frequency domain and ultrasound imaging. Acad Radiol 21:263-70
Ambrosone, Christine B; Young, Allyson C; Sucheston, Lara E et al. (2014) Genome-wide methylation patterns provide insight into differences in breast tumor biology between American women of African and European ancestry. Oncotarget 5:237-48
O'Brien, Shalana; Golubovskaya, Vita M; Conroy, Jeffrey et al. (2014) FAK inhibition with small molecule inhibitor Y15 decreases viability, clonogenicity, and cell attachment in thyroid cancer cell lines and synergizes with targeted therapeutics. Oncotarget 5:7945-59

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