In the 1970's and early 1980's hyperthermia was shown to have substantial potential to increase the curability of human cancer because preclinical studies of the interaction between hyperthermia and x-irradiation or anticancer drugs were so compellingly positive. To date, hyperthermia may have been shown to increase radiotherapeutic control of breast cancer recurrent on the chest wall and large neck nodes from head and neck cancers, but an impact on curability (i.e. overall survival) of patients with these or other tumors has not been documented. We believe that the reasons why hyperthermia has not reached its full clinical potential are because both its biological interactions and the physics of its delivery have yet to be optimized. Both of these factors will be addressed in the work proposed in this application. The interrelated Projects in this program will attempt to improve the clinically useful biology of hyperthermia by: 1) better defining the mechanisms responsible for thermotolerance so that we can attempt to selectively inhibit thermotolerance development in malignant tissues, and, thus, make more frequent fractionation of hyperthermia rational (Dr. Calderwood, Project I); 2) exploring whole body hyperthermia (WBH) as one of a series of positive modulators of anticancer alkylating agents (AA's) + local radiation in sophisticated animal models (Dr. Teicher, Project II); and 3) continuing to develop maximally effective combinations of anticancer drugs, local radiation and hyperthermia in the clinic (Dr. Herman, Project V). The Program Project will also attempt to improve the physics of hyperthermia delivery by: 1) testing and refining the capabilities of a new Focused, Segmented Ultrasound Machine (FSUM) in the clinic (Dr. Herman, Project V); 2) developing new 3-D computer modelling capabilities to interface with FSUM (Dr. Svensson, Project III); 3) utilizing interstitial probes which can measure tissue temperatures densely as well as tissue perfusion (Dr. Bowman, Project IVa); and 4) developing simplified 3-D temperature models which can be used in real time to improve patient treatments with the FSUM (Dr. Newman, Project IVb).

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (SRC (J1))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Dana-Farber Cancer Institute
United States
Zip Code
Hurwitz, Mark D; Hansen, Jorgen L; Prokopios-Davos, Savina et al. (2011) Hyperthermia combined with radiation for the treatment of locally advanced prostate cancer: long-term results from Dana-Farber Cancer Institute study 94-153. Cancer 117:510-6
Wang, XiaoZhe; Khaleque, Md Abdul; Zhao, Mei Juan et al. (2006) Phosphorylation of HSF1 by MAPK-activated protein kinase 2 on serine 121, inhibits transcriptional activity and promotes HSP90 binding. J Biol Chem 281:782-91
Hurwitz, Mark D; Kaplan, Irving D; Hansen, Jorgen L et al. (2005) Hyperthermia combined with radiation in treatment of locally advanced prostate cancer is associated with a favourable toxicity profile. Int J Hyperthermia 21:649-56
Calderwood, Stuart K (2005) Regulatory interfaces between the stress protein response and other gene expression programs in the cell. Methods 35:139-48
Calderwood, Stuart K; Theriault, Jimmy R; Gong, Jianlin (2005) How is the immune response affected by hyperthermia and heat shock proteins? Int J Hyperthermia 21:713-6
Calderwood, S K (2005) Evolving connections between molecular chaperones and neuronal function. Int J Hyperthermia 21:375-8
Tang, Dan; Khaleque, Md Abdul; Jones, Ellen L et al. (2005) Expression of heat shock proteins and heat shock protein messenger ribonucleic acid in human prostate carcinoma in vitro and in tumors in vivo. Cell Stress Chaperones 10:46-58
Calderwood, Stuart K; Theriault, Jimmy R; Gong, Jianlin (2005) Message in a bottle: role of the 70-kDa heat shock protein family in anti-tumor immunity. Eur J Immunol 35:2518-27
Ciocca, Daniel R; Calderwood, Stuart K (2005) Heat shock proteins in cancer: diagnostic, prognostic, predictive, and treatment implications. Cell Stress Chaperones 10:86-103
Tonkiss, J; Calderwood, S K (2005) Regulation of heat shock gene transcription in neuronal cells. Int J Hyperthermia 21:433-44

Showing the most recent 10 out of 52 publications