Radiation modifiers, including hyperbaric oxygen, chemical radiosensitizers, normal tissue protective agents, and local and systemic hyperthermia are continually being investigated. A <b>radiosensitizer</b> is a compound that would make tumor cells more sensitive to the effects of radiation, and have no effect upon normal cells. This would allow a given dose of radiation to have a greater effect upon the malignant tissue. Some radiosensitizers lead to an increase in sensitivity of the hypoxic and therefore radioresistant parts of tumours against X- and gamma-radiation. With sufficient concentration within the tumour, they can act where the radiation can reach, even in the deeper parts of the body. 

A number of chemical compounds that modify radiation effects have been discovered and tested both in the laboratory and clinically over the past 25 years. There are classes of compounds: aminothiol radio-protectors which act on well vascularized oxygenated cells and concentrate in tissues such as skin, gut and marrow; nitromidazole radiosensitizers [metoclopramide derivatives, which cause DNA strand breaks and inhibit DNA repair, and thereby sensitizes radiation and chemotherapeutic drugs in human tumor cell cultures]; pyrimidine analogues which are incorporated into the DNA of cycling cells and cause radiosensitization; and cancer themotherapy agents which, in addition to their ability to kill tumor cells directly, also may sensitize tumor and normal cells to radiation. In addition, 2-deoxy-D-glucose prevents efficient utilization of glucose in cells, and has a greater effect on tumor cells. Not being able to generate energy from glucose inhibits the repair of radiation damage preferentially in tumor cells.

Tumor damage depends upon amount of hypoxic cells [which are radioresistant], radiation dose, doses of chemotherapy and/or other radiosensitizer given, ambient temperature, timing of drug dose and radiation exposures. The effectiveness of oxygenating the hypoxic cells to make them radiosensitive depends upon how densely the tissue is vascularized, hemoglobin concentrations and affinities for oxygen, and levels of carbon dioxide breathed in [causes blood vessels to dilate and deliver more blood to tissues], as well as use of hyperbaric [high pressure] oxygen treatment.

Radiotherapy combined with razoxane [a radiosensitizer] seems to improve the local control in inoperable, residual, or recurrent Soft Tissue Sarcoma compared to radiotherapy alone. The combined treatment is a fairly well tolerated procedure at low costs. It can be recommended for inoperable primary Soft Tissue Sarcoma or gross disease after incomplete resection, conditions that are associated with limited local control and a grave prognosis

COX-2 9 (Cyclooxygenase-2) is overexpressed in many types of malignant tumors. It mediates production of prostaglandins, which in turn may stimulate tumor growth and protect against damage by cytotoxic agents. Treatment with a selective inhibitor of COX-2 [like Vioxx or Celebrex] may greatly enhance tumor radioresponse without markedly affecting normal tissue radioresponse. COX-2 inhibitors might have marked value for increasing the therapy/damage ratio of irradiation.
 
&&url
&&url