Researchers at the Foundation recently launched a new study to further investigate the effectiveness of hyperthermia (hyperthermic perfusion) as an anticancer treatment. Dr. Giovanella and his will selectively heat the cells in human cancer tumors grown in the laboratory’s athymic mice in a way that causes complete destruction of the cancer.
The new research will begin by injecting nanoparticles coated with monoclonal antibodies designed to latch onto target cancer cells. When the nanoparticles are subsequently exposed to a radiofrequency field, they absorb and emit the energy as heat, raising temperatures in the tumor cells.
Research will initially concentrate on human breast cancer tumors that overexpress the HER2/neu protein. These tumors comprise about 20 percent of the clinical volume of all breast cancers. An antibody to this protein already exists in the form of Herceptin, an anticancer drug that has proved effective against certain aggressive breast cancers. This drug will be used to coat the nanoparticles prior to radiofrequency exposure.
Tracking Results
By labeling the Herceptin with radioactive iodine, Foundation scientists will be able to follow the distribution of the nanoparticles through the mouse system. Specially-designed heat probes will measure and record the real time temperature within the primary tumor and the normal tissue.
The initial objective is to maintain elevated temperatures of 45-46° C in the tumor and 37° C in the surrounding tissues. But temperatures, combined with levels of chemotherapy, will be adjusted to achieve optimal results – the complete destruction of tumors and minimal incidence of recurrence.
If results are as expected, the Foundation will expand its hyperthermia investigations. Application will be made to conduct clinical trials in humans of the new treatment. Also, other tumors and other biomarkers (beyond HER2) will be researched. Though not a new concept, the use of nanoparticles has infused new hope into hyperthermia as a more effective cancer treatment.
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Normal breast tissue cells, and most tumor cells, have only one copy of each of the HER2 gene. This gene produces a few protein receptors on the cell’s surface, which regulates important cell functions, such as division and adhesion. The receptor is stimulated by growth factors. In about 20% of breast cancers, tumor cells have multiple copies of the gene that regulates the growth factor. These multi-copy gene celles are very malignant because they “overexpress” HER2/neu receptors creating an explosive cell growth potential with each gene capable of creating up to six receptors.