Drug persistence – From antibiotics to cancer therapies. Issue 10 (August 2018)

• Record Type: Journal Article
• Authors: Kochanowski, Karl; Morinishi, Leanna; Altschuler, Steven J.; Wu, Lani F.
• Is Part Of: Current opinion in systems biology. Issue 10(2018)
• Page Start: 1
• Page End: 8
• Publication Date: 2018-08
• Subjects: Persister -- Antibiotics -- Bacteria -- Cancer therapy; Systems biology -- Periodicals; 570
• DOI: 10.1016/j.coisb.2018.03.003
• Languages: English
• ISSNs: 2452-3100

Abstract

Abstract: Drug-insensitive tumor subpopulations remain a significant barrier to effective cancer treatment. Recent works suggest that within isogenic drug-sensitive cancer populations, subsets of cells can enter a 'persister' state allowing them to survive prolonged drug treatment. Such persisters are well-described in antibiotic-treated bacterial populations. In this review, we compare mechanisms of drug persistence in bacteria and cancer. Both bacterial and cancer persisters are associated with slow-growing phenotypes, are metabolically distinct from non-persisters, and depend on the activation of specific regulatory programs. Moreover, evidence suggests that bacterial and cancer persisters are an important reservoir for the emergence of drug-resistant mutants. The emerging parallels between persistence in bacteria and cancer can guide efforts to untangle mechanistic links between growth, metabolism, and cellular regulation, and reveal exploitable therapeutic vulnerabilities. Highlights: Drug persistence is frequently observed in bacterial and cancer cell populations. Slow growth, and a distinct metabolic and regulatory state are common persister hallmarks. It is unclear how growth, metabolism, and regulation are linked mechanistically in cancer persisters. Persisters can serve as a reservoir for the emergence of resistant mutants. Targeting distinct persister vulnerabilities may provide new therapeutic avenues.