Looking for driver pathways of acquired resistance to targeted therapy: Drug resistant subclone generation and sensitivity restoring by gene knock-down

Chiara Arienti, Sara Pignatta, Michele Zanoni, Michela Cortesi, Alice Zamagni, Filippo Piccinini, Anna Tesei

Research output: Contribution to journalArticle

Abstract

The past two decades have seen a shift from cytotoxic drugs to targeted therapy in medical oncology. Although targeted therapeutic agents have shown more impressive clinical efficacy and minimized adverse effects than traditional treatments, drug resistance has become the main limitation to their benefits. Several preclinical in vitro/in vivo models of acquired resistance to targeted agents in clinical practice have been developed mainly by using two strategies: i) genetic manipulation for modeling genotypes of acquired resistance, and ii) in vitro/in vivo selection of resistant models. In the present work, we propose a unifying framework, for investigating the underlying mechanisms responsible for acquired resistance to targeted therapeutic agents, starting from the generation of drug-resistant cellular subclones to the description of silencing procedures used for restoring the sensitivity to the inhibitor. This simple time- and cost-effective approach is widely applicable, and could be easily extended to investigate resistance mechanisms to other targeted therapeutic drugs in different tumor histotypes.

Original languageEnglish
Article number56583
JournalJournal of Visualized Experiments
Volume2017
Issue number130
DOIs
Publication statusPublished - Dec 11 2017

Keywords

  • Cancer biology
  • Clonogenic assay
  • Drug resistance
  • In vitro model
  • Issue 130
  • Re-sensitization
  • siRNA transfection
  • Targeted therapy

ASJC Scopus subject areas

  • Neuroscience(all)
  • Chemical Engineering(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Fingerprint Dive into the research topics of 'Looking for driver pathways of acquired resistance to targeted therapy: Drug resistant subclone generation and sensitivity restoring by gene knock-down'. Together they form a unique fingerprint.

  • Cite this