Diverse drug-resistance mechanisms can emerge from drug-tolerant cancer persister cells

Cancer therapy has traditionally focused on eliminating fast-growing populations of cells. Yet, an increasing body of evidence suggests that small subpopulations of cancer cells can evade strong selective drug pressure by entering a 'persister' state of negligible growth. This drug-tolerant state has been hypothesized to be part of an initial strategy towards eventual acquisition of bona fide drug-resistance mechanisms. However, the diversity of drug-resistance mechanisms that can expand from a persister bottleneck is unknown. Here we compare persister-derived, erlotinib-resistant colonies that arose from a single, EGFR-addicted lung cancer cell. We find, using a combination of large-scale drug screening and…

• WF
  Welch Foundation

  Award: I-1644
• CP
  Cancer Prevention and Research Institute of Texas

  Award: RP110708
• NI
  National Institutes of Health

  Awards: 1P30CA142543, NIH R01, CA185404
• UO
  University of Texas MD Anderson Cancer Center
• UO
  University of California, San Francisco
• NC
  National Cancer Institute

  Awards: CA185404, 1P30CA142543, 1P30CA142543-01