CANCER COMBINATION CHEMOTHERAPY WITH RETINOIDS - EXPERIMENTAL RATIONALE

Retinoids, cytokines as well as 1,25-dihydroxyvitamin D-3 and its anal ogs are all classes of compounds with pleiotropic actions. They inhibi t proliferation in human transformed epithelial cell lines and induce differentiation in human transformed hemopoietic cell lines. In a muri ne model of tumor cell-induced angiogenesis all three classes of compo unds inhibit the formation of new blood vessels, necessary for supplyi ng the growing tumor with oxygen and nutrients. Combinations of compou nds from the three different classes lead to higher efficacy than the compounds administered as single agents. The effects of combinations v ary depending on the individual representatives of the three classes a nd on the particular test models used. Additive, synergistic and poten tiating effects have been observed. The results obtained in experiment al systems raise hope that combination therapy might be useful in the treatment of certain human neoplastic diseases.