Uncovering scaling laws to infer multidrug response of resistant microbes and cancer cells.

Published

Journal Article

Drug resistance in bacterial infections and cancers constitutes a major threat to human health. Treatments often include several interacting drugs, but even potent therapies can become ineffective in resistant mutants. Here, we simplify the picture of drug resistance by identifying scaling laws that unify the multidrug responses of drug-sensitive and -resistant cells. On the basis of these scaling relationships, we are able to infer the two-drug response of resistant mutants in previously unsampled regions of dosage space in clinically relevant microbes such as E. coli, E. faecalis, S. aureus, and S. cerevisiae as well as human non-small-cell lung cancer, melanoma, and breast cancer stem cells. Importantly, we find that scaling relations also apply across evolutionarily close strains. Finally, scaling allows one to rapidly identify new drug combinations and predict potent dosage regimes for targeting resistant mutants without any prior mechanistic knowledge about the specific resistance mechanism.

Full Text

Duke Authors

Cited Authors

  • Wood, KB; Wood, KC; Nishida, S; Cluzel, P

Published Date

  • March 27, 2014

Published In

Volume / Issue

  • 6 / 6

Start / End Page

  • 1073 - 1084

PubMed ID

  • 24613352

Pubmed Central ID

  • 24613352

Electronic International Standard Serial Number (EISSN)

  • 2211-1247

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2014.02.007

Language

  • eng

Conference Location

  • United States