It has been appreciated for more than 50 years that very low levels of oxygenation, or
hypoxia, both protect cells from killing by X-irradiation and are present in solid
tumors but not in normal tissues. Until recently, however, there has been no definitive proof that
hypoxia in human
tumors contributes to
radiotherapy treatment failure. We now know that
hypoxia in solid
tumors is not only a major problem for
radiation therapy but also leads to resistance to most anticancer drugs and, importantly, appears to accelerate malignant progression and increase
metastasis. To date, efforts to overcome the problem of
hypoxia have had only limited success. However, the recent development of new drugs that are nontoxic until they are activated in the hypoxic cell opens a new era. The first of these new drugs to be tested clinically,
tirapazamine, a
drug that is highly toxic to hypoxic but not aerobic cells, has already demonstrated efficacy in selective potentiation of
cisplatin in randomized Phase III trials with
non-small cell lung cancer. The unique presence of hypoxic cells in human
tumors provides an important target for selective
cancer therapy.