Overview

Breast cancer and prostate cancer are representative of mutations of oncogenes, antioncogenes and other genes crucial to the regulation of pivotal cell functions. Thus, hormone-dependent cancers, the proliferation and sometimes even survival of which require actions of estrogen refractoriness has been explained by the de novo occurrence of such mutations and subsequent selection of cells and androgen, respectively. Therefore, administration of antiestrogen or antiandrogen drugs causes a good clinical with these newly mutated genes. In view of the fact that antihormone treatment is more effective in cancers posiresponse in a certain proportion of patients with these cancers. Quite an embarrassing problem, however, is the tive for respective hormone receptors, and hormone dependency relates directly to the hormone action that fact that the beneficial effects of antihormones are limited in duration (fig. 1). In other words, these cancers become involves the receptors, the latter have been considered a potential target of such mutations. This is also the case refractory to treatment with antihormones. The events underlying the phenomenon of refractories consist of at because hormone receptors are the only well-documented proteins for the steps of hormone action. Thus, the search least two mutually related processes. For one thing, cancers which have been able to grow only in the presence for mutations has been focused on the genes for hormone receptors. In some cases, such mutations that explain of hormone before treatment (hormone-dependent) now attain the potential to proliferate in the absence of it the advent of hormone independence and antihormone dependence were found in genes for hormone receptors. (hormone-independent). And second, in addition to the apparent independence, these cancers paradoxically beHowever, it turned out that most of the time, refractoriness develops even in the absence of mutations in the come dependent on the antihormones. Antihormones, once having prevented cancer growth, now turn out to receptor genes. Therefore, it is very clear now that we should look for changes in other factors involved in horpositively support growth. Consequently, if antihormones are withdrawn when patients become refractory to treatmone action, especially those directly or indirectly connected to the regulation of cell cycle and apoptosis. ment, some cancers respond with a transient decline in growth; a phenomenon known as the withdrawal synThe following experiences and observations do not support the gene mutation as a general cause of the occurdrome. Then, after a while, the cancers start to regrow as actively as they did before treatment or more aggressively rence of refractoriness and paradoxical dependency. (1) The temporal profile, as shown in figure 1, of the most of the time. These changes in biological properties of cancers develop during the course of anticancer treatment response in cancer patients to antihormone treatment is rather common among various hormone-dependent with antihormones. Thus, the next effort we clinical oncologists should exert is to elucidate the mechanism for the cancers. Thus, in the case of prostate cancer, more than 80% of patients respond to antiandrogen treatment, and development of refractoriness and paradoxical dependence on antihormones, and to develop a means of prethen almost regularly most of the patients become refractory to the treatment during the course of a few years. venting the advent of these changes. Processes in the development and progression of canA similar tendency has been observed in patients with breast cancer who were treated with antiestrogen drugs. cers have been explained by an accumulation of a series of