Pharmacology and clinical investigation of SR-2508 (etanidazole)

Abstract

The common, slow-growing solid tumors remain refractory to current chem-otherapeutic strategies. Resistance appears, in part, to be a consequence of the abnormal metabolic environment of solid tumors. It is proposed that the disordered vascular development in the growing tumor mass results in a proportion of cells being remote from capillaries; the increased diffusion distance leads to hypoxia, low glucose concentrations, and reduced cellular pH [reviewed in 1]. Cells in this hypoxic environment pose a particular problem, because while quiescent under hypoxic conditions, they may be recruited into the proliferative fraction as a tumor shrinks in response to therapy. Tumor regrowth during reoxygenation following radiation therapy illustrates this phenomenon. It has long been recognized that in their quiescent state, hypoxic cells are resistant both to radiation and to electrophilic cytotoxic drug [2,3]. The proportion of hypoxic cells in a tumor is in part a function of tumor size; but even small tumors (1 mm in diameter) may have hypoxic fractions ranging from 10 to 30% [4]. The tumor types in which significant hypoxic fractions have been identified include all the common solid tumors, especially lung, colon, head and neck, and breast cancers [5].KeywordsTotal Body ClearanceHypoxic CellPeripheral Mononuclear CellHypoxic FractionSR2508 TreatmentThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.