Overcoming multidrug resistance in cancer with dirty drugs

Event Details

  • Date:
  • Venue: PCB - Auditorium
  • Address: C/Baldiri i Reixach, 4-8, 08028 Barcelona
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IRB BioMed Seminars


by Óscar Fernández-Capetillo, PhD – Group Leader Genomic Instability Group – Director Molecular Oncology Programme, CNIO, Madrid, Spain.



Resistance to therapies, intrinsic or acquired during treatment, is a major medical problem that limits the efficacy of our current anti-cancer armamentarium. Unfortunately, while some of the mechanisms that contribute to resistance are known, our knowledge of this phenomenon, particularly for the case of multi-drug resistance (MDR), remains incomplete. Through genome-wide genetic screens and bioinformatic analyses, we discovered that one of the most frequent mutations in cancer, FBXW7 deficiency, confers a very severe MDR phenotype to cancer cells. Interestingly, we later found that these MDR is associated to an increase in mitochondrial activity, which was previously linked to resistance by other groups. While we do not understand how mitochondrial function relates to MDR, it offered us a vulnerability that can be exploited. Accordingly, therapies that target mitochondria are particularly toxic for FBXW7 deficient cells. Finally, when looking for additional drugs that could overcome the MDR of FBXW7 mutant cells through bioinformatics, we discovered a group of seeming unrelated multi-kinase inhibitors that were able to do it. Interestingly, these compounds are “dirty” drugs that are often used in the clinic, even though their actual target is unknown. We believe we have discovered an alternative model that explains why these drugs kill cancer cells. But if you want to know about it, you will have to come to my seminar.


IRB BioMed Seminars

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