2,4-dinitro-5-ethyleneiminobenzamide (CB 1954): a potent and selective inhibitor of the growth of the Walker carcinoma 256.
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Biomedical subjects
Publications and source records attributed to T A Connors.
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Despite extensive clinical trials, mortality from colon cancer has remained essentially unchanged since the 1950s. However, the increasing numbers of complete and partial responses seen in clinical trials suggest that colon cancer can be successfully treated by chemotherapy, but only if the antitumour selectivity can be increased by a substantial amount. This will be possible by the introduction of new drugs with more precise mechanisms of action, such as those acting specifically on signalling or cell cycle control pathways shown to be aberrant in colon cancer. Alternatively, the selectivity of present day agents may be increased considerably by the selective activation of prodrugs in tumours (ADEPT) or by targeting them to tumours using polymers. Other new approaches using vaccines or some form of gene therapy will potentiate present chemotherapy, while the introduction of positron emission tomography (PET) scanning will allow the rapid detection of agents with activity that would have been missed by conventional measurements of response.
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Human lung, ovarian, colonic, and renal carcinomas have been grown in mice artificially deprived of T-lymphocytes. All grew slowly and were shown to have a human karyotype even after several transplant generations. Their responses to chemotherapy were similar to the expected clinical response with the important exception of hexamethylmelamine which caused complete regression of two lung carcinomas (even when weighing up to 2.5 g at the start of treatment) and a renal carcinoma, while completely inhibiting the growth of an ovarian carcinoma and another lung carcinoma. Measurement of plasma carcinoembryonic antigen levels proved to be of value in assessing drug efficacy.