Tolerant/Persister Cancer Cells and the Path to Resistance to Targeted Therapy

Mirna Swayden, Houssein Chhouri, Youssef Anouar, Luca Grumolato

Research output: Contribution to journalReview articlepeer-review

17 Scopus citations


The capacity of cancer to adapt to treatment and evolve is a major limitation for targeted therapies. While the role of new acquired mutations is well-established, recent findings indicate that resistance can also arise from subpopulations of tolerant/persister cells that survive in the presence of the treatment. Different processes contribute to the emergence of these cells, including pathway rebound through the release of negative feedback loops, transcriptional rewiring mediated by chromatin remodeling and autocrine/paracrine communication among tumor cells and within the tumor microenvironment. In this review, we discuss the non-genetic mechanisms that eventually result in cancer resistance to targeted therapies, with a special focus on those involving changes in gene expression.

Original languageEnglish
Issue number12
StatePublished - 4 Dec 2020
Externally publishedYes


  • BRAF
  • EGFR
  • cell signaling
  • drug resistance
  • intratumor heterogeneity
  • lung cancer
  • melanoma
  • targeted therapy
  • tolerant and persister cells


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