The ultimate objective of this work is to develop a non-invasive means of enhancing the efficacy of anti-cancer agents, including chemotherapeutic drugs and x-ray irradiation. This approach is based on our preliminary data, which indicate that electromagnetic fields (EMFs), depending on exposure conditions, can either increase or decrease the synthesis of stress proteins within cells. Stress proteins play a major role in protecting cells from damage. We hypothesize that by decreasing the level of stress proteins and thus lowering cytoprotection within a cancer cell, the cell will be made more susceptible to subsequent treatment with anti-cancer agents. Clinically, this means that a lower dose of anti-cancer agent should effect a greater cancer cell killing. By the same reasoning, lower doses of the anti-cancer treatment adjuvant with EMF exposure should yield equivalent killing as higher doses without EMF exposure. This translates into fewer side effects as a result of the treatment. Further, we have developed techniques for focusing the action of an EMF, such that only the volume of the tumor, and not the surrounding or intervening tissue is affected by the fields. This means that only the tumor mass is made more susceptible to the treatment. This is extremely important, because use of focused EMF adjuvant with anti-cancer treatments could permit a lowered dose of an anti-cancer agent to have the same effect. This is especially critical for chemotherapeutic agents which have significant normal cell toxicity, leading to substantial side effects during treatment. In some instances, the dose of a drug needed to effectively eliminate a cancer mass is prohibitive because of serious side effects such as heart damage and severe anemia. To validate that EMF exposures can have either beneficial or adverse effects in cancer therapy, and advance their use to the status of accepted medical practice, this work aims to accumulate reliable data in tumor cell culture models. By the end of the requested funding, we hope to have developed a clinically-relevant model for the use of EMFs, which can then be translated into animal studies. To achieve this, we will apply EMFs as an adjuvant with chemotherapy or x-ray, and determine which classes of chemotherapeutic agents are most responsive to EMF intervention. Further, we will determine the EMF parameters necessary to maximize EMF effects in chemotherapy or x-ray irradiation. ? ?