Unknown

Dataset Information

0

Liposomal formulation of HIF-1α inhibitor echinomycin eliminates established metastases of triple-negative breast cancer.


ABSTRACT: Hypoxia-inducible factor 1α (HIF-1α) is recognized as a prime molecular target for metastatic cancer. However, no specific HIF-1α inhibitor has been approved for clinical use. Here, we demonstrated that in vivo efficacy of echinomycin in solid tumors with HIF-1α overexpression is formulation-dependent. Compared to previously-used Cremophor-formulated echinomycin, which was toxic and ineffective in clinical trials, liposomal-echinomycin provides significantly more inhibition of primary tumor growth and only liposome-formulated echinomycin can eliminate established triple-negative breast cancer (TNBC) metastases, which are the leading cause of death from breast cancer, as available therapies remain minimally effective at this stage. Pharmacodynamic analyses reveal liposomal-echinomycin more potently inhibits HIF-1α transcriptional activity in primary and metastasized TNBC cells in vivo, the latter of which are HIF-1α enriched. The data suggest that nanoliposomal-echinomycin can provide safe and effective therapeutic HIF-1α inhibition and could represent the most potent HIF-1α inhibitor in prospective trials for metastatic cancer.

SUBMITTER: Bailey CM 

PROVIDER: S-EPMC7508926 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC7291851 | biostudies-literature
| S-EPMC8746909 | biostudies-literature
| S-EPMC9403568 | biostudies-literature
| S-EPMC8345094 | biostudies-literature
| S-EPMC7774020 | biostudies-literature
| S-EPMC5652730 | biostudies-literature
| S-EPMC7768086 | biostudies-literature
| S-EPMC7481213 | biostudies-literature
| S-EPMC6821315 | biostudies-literature
| S-EPMC6416729 | biostudies-literature