Ras protein, for example, is central amongst the many oncogene(“cancer-producing
gene”) encoded proteins that relay signals from the exterior of the cell to the cell nucleus.
In normal cells, ras protein controls the “switch” for normal cellular growth and differ-
entiation by cycling GTP and GDP by a hydrolytic process. Oncogenic ras proteins
have lost this hydrolytic capacity, thereby leaving the cellular growth “switched on.”
Modification of ras protein represents a logical point of molecular attack in drug design.
7.8.5.4 Hormonal Therapy
Tumors that occur in biochemically unique organs offer an opportunity for biochemically
unique approaches—the potential to design drugs with reduced toxicity. Hormonal
manipulation has been employed successfully for a number of years to treat cancer in
gender-specific organ systems. This approach is predicated on the observation that such
tumors express hormonal receptors on their cell surfaces and that the tumor’s biochem-
istry is thus susceptible to hormone manipulation. The clinical usefulness of antiestro-
gens in treating breast cancer and antiandrogens for prostate cancer is well recognized.
Gonadrotropin-releasing hormone (GnRH) agonists have also been used in hormone-
responsive cancers. A logical extension of hormonal therapy is to block the biosynthesis
of the hormones that may be influencing tumor growth. Aromatase enzyme inhibitors
are an excellent example of this approach. A major step in estrogen biosynthesis involves
the aromatase-catalyzed conversion of androstenedione to estrone; blocking the aromatase
enzyme lowers the level of circulating estradiol. Two aromatase inhibitors, anastrazole
(7.96) and letrozole (7.97), have been evaluated in the treatment of metastatic breast cancer.
Recently, some clinical trials have suggested the use of anastrazole before tamoxifen for
post-menopausal women with metastatic breast cancer.
7.8.5.5 Photodynamic Therapy
Since not all tissues are as biochemically unique as hormone-secreting organs, other
approaches have been explored in an attempt to achieve tumor-specific killing while spar-
ing other tissues. Photodynamic therapy is such an approach. This type of therapy is based
upon the accumulation of a drug molecule within the tumor, followed by a light-mediated
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