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 membrane - impermeant compounds , which inhibit the enzymatic activity of mn protein / polypeptides and that are useful for treating patients with preneoplastic / neoplastic disease . further methods are disclosed for the preparation of positively - charged , membrane - impermeant heterocyclic sulfonamide ca inhibitors with high affinity for the membrane - bound carbonic anhydrase ca ix . preferred ca ix - specific inhibitors are aromatic and heterocylic sulfonamides , preferably that are membrane - impermeant . particularly preferred ca ix - specific inhibitors are pyridinium derivatives of such aromatic and heterocyclic sulfonamides . the ca ix - specific inhibitors of the invention can also be used diagnostically / prognostically for preneoplastic / neoplastic disease , and for imaging use , for example , to detect precancerous cells , tumors and / or metastases . the ca ix - specific inhibitors can be labelled or conjugated to radioisotopes for radiotherapy . the ca ix - specific inhibitors may be combined with conventional therapeutic anti - cancer drugs , with other different inhibitors of cancer - related pathways , with bioreductive drugs , or with radiotherapy to enhance the efficiency of each treatment . the ca ix - specific inhibitors may also be combined with ca ix - specific antibodies , preferably monoclonal antibodies or biologically active antibody fragments , more preferably humanized or fully human ca ix monoclonal antibodies or biologically active fragments or such monoclonal antibodies . still further , the ca ix - specific inhibitors can be used for gene therapy coupled to vectors for targeted delivery to preneoplastic / neoplastic cells expressing ca ix on their surfaces .