[en] Many solid tumors are characterized by spatiotemporal heterologous supply conditions due to a histomorphological and functional disaster of their vascular network. Hypoxia as a pathophysiologic consequence is a well-established, yet still not entirely understood direct radioresistance factor while other milieu conditions such as tissue acidosis and lactate accumulation are considered only as indirect modulators of tumor radioresponse. An enhanced level of local and overall lactate in tumor tissues may result from the pathologic vascular supply as oxygen deficiency leads to an increased cellular glycolytic flux but disposal of waste products is impeded. In addition, genetic alterations as a consequence of malignant transformation are known to contribute to lactate accumulation under aerobic conditions in tumors. This may be true for genes (i) which control the expression or activity of glycolytic enzymes and related transporters and/or (ii) which lead to a truncated citric acid cycle and which support glutaminolysis. In various tumor entities including squamous cell carcinomas of head and neck and adenocarcinomas of the rectum high lactate concentrations (> 8-10 mM as compared to normal tissues with ∼ 2 mM) were shown to correlate with risk of metastases and/or reduced recurrence-free as well as overall survival. Several in vitro studies show adverse effects of high lactate concentrations on various tumor stromal cell types that may contribute to this phenomenon. Also, most recently, a hypoxia-independent correlation of lactate level with radioresistance was documented in a subcutanous xenograft mouse model of human squamous cell carcinomas indicating that lactate could causally and/or directly relate to radioresponse. The present study was performed to evaluate the impact of pathophysiological, high extracellular lactate levels and reduced pH on the survival and radioresponse of various established cancer cell lines in a classical in vitro assay