Metronomic chemotherapy offsets HIF? induction upon maximum-tolerated dose in metastatic cancers

ABSTRACT: Conventional maximum tolerated dose (MTD) chemotherapy relies on periodic, massive cancer cell ablation events followed by treatment-free intermissions, stereotypically resulting in resistance, relapse, and mortality. Furthermore, MTD chemotherapy can promote metastatic dissemination via activation of a transcriptional program dependent on hypoxia-inducible factor (HIF)-1? and -2? (hereafter referred to as HIF?). Instead, frequent low-dose metronomic (LDM) chemotherapy displays less adverse effects whilst preserving significant pre-clinical anticancer activity. Consequently, we hereby compared the effect of MTD or LDM chemotherapy upon HIF? in models of advanced, metastatic colon and breast cancer. Our results revealed that LDM chemotherapy can offset paralog-specific, MTD-dependent HIF? i

SUBMITTER: Dr. Luana Schito 

PROVIDER: S-SCDT-EMM-2019-11416 | biostudies-other |

REPOSITORIES: biostudies-other