Therapeutic methods for inhibiting the growth of preneoplastic / neoplastic
vertebrate cells that abnormally express MN
protein are disclosed. Screening assays are provided for identifying compounds, preferably organic compounds, preferably aromatic and heterocylic sulfonamides, which inhibit the enzymatic activity of MN / CA IX and that are useful for treating patients with preneoplastic /
neoplastic disease. Further, the CA IX-specific inhibitors when labeled or linked to an appropriate visualizing means can also be used diagnostically / prognostically for preneoplastic /
neoplastic disease, and for imaging use, for example, to detect hypoxic
precancerous cells, tumors and / or metastases, by selectively binding to activated CA IX, preferably CA IX activated under hypoxic conditions, and not to inactive CA IX. Such detection of hypoxic conditions can be helpful in determining
effective treatment options, and in predicting
treatment outcome and the prognosis of
disease development. Still further, the CA IX-specific inhibitors can be used therapeutically to selectively target hypoxic cells expressing activated CA IX. The CA IX-specific inhibitors can be labelled or conjugated to radioisotopes for radiotherapy of hypoxic cells. Alternatively, the CA IX-specific inhibitors can be used for
gene therapy coupled to vectors for targeted delivery to hypoxic preneoplastic / neoplastic cells expressing activated CA IX on their surfaces. In an alternative mode of the invention, CA IX-specific inhibitors may be used therapeutically to target acidic conditions of a tumor, e.g., to increase pHe in order to enhance the
efficacy of
weak base chemotherapeutic drugs.