Micrornas as predictive biomarkers of resistance to targeted therapies in gastrointestinal tumors

Valentina Angerilli, Francesca Galuppini, Gianluca Businello, Luca Dal Santo, Edoardo Savarino, Stefano Realdon, Vincenza Guzzardo, Lorenzo Nicolè, Vanni Lazzarin, Sara Lonardi, Fotios Loupakis, Matteo Fassan

Research output: Contribution to journalReview articlepeer-review


The advent of precision therapies against specific gene alterations characterizing different neoplasms is revolutionizing the oncology field, opening novel treatment scenarios. However, the onset of resistance mechanisms put in place by the tumor is increasingly emerging, making the use of these drugs ineffective over time. Therefore, the search for indicators that can monitor the development of resistance mechanisms and above all ways to overcome it, is increasingly important. In this scenario, microRNAs are ideal candidate biomarkers, being crucial post-transcriptional regulators of gene expression with a well-known role in mediating mechanisms of drug resistance. Moreover, as microRNAs are stable molecules, easily detectable in tissues and biofluids, they are the ideal candidate biomarker to identify patients with primary resistance to a specific targeted therapy and those who have developed acquired resistance. The aim of this review is to summarize the major studies that have investigated the role of microRNAs as mediators of resistance to targeted therapies currently in use in gastro-intestinal neoplasms, namely anti-EGFR, anti-HER2 and anti-VEGF antibodies, small-molecule tyrosine kinase inhibitors and immune checkpoint inhibitors. For every microRNA and microRNA signature analyzed, the putative mechanisms underlying drug resistance were outlined and the potential to be translated in clinical practice was evaluated.

Original languageEnglish
Article number318
Pages (from-to)1-19
Number of pages19
Issue number3
Publication statusPublished - Mar 21 2021


  • Drug resistance
  • GI cancers
  • MicroRNAs
  • Targeted therapy

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)


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