Repurposing old drugs to fight multidrug resistant cancers

Jelena Dinić, Thomas Efferth, Alfonso T. García-Sosa, Jelena Grahovac, José M. Padrón, Ilza Pajeva, Flavio Rizzolio, Simona Saponara, Gabriella Spengler, Ivanka Tsakovska

Research output: Contribution to journalReview article

Abstract

Overcoming multidrug resistance represents a major challenge for cancer treatment. In the search for new chemotherapeutics to treat malignant diseases, drug repurposing gained a tremendous interest during the past years. Repositioning candidates have often emerged through several stages of clinical drug development, and may even be marketed, thus attracting the attention and interest of pharmaceutical companies as well as regulatory agencies. Typically, drug repositioning has been serendipitous, using undesired side effects of small molecule drugs to exploit new disease indications. As bioinformatics gain increasing popularity as an integral component of drug discovery, more rational approaches are needed. Herein, we show some practical examples of in silico approaches such as pharmacophore modelling, as well as pharmacophore- and docking-based virtual screening for a fast and cost-effective repurposing of small molecule drugs against multidrug resistant cancers. We provide a timely and comprehensive overview of compounds with considerable potential to be repositioned for cancer therapeutics. These drugs are from diverse chemotherapeutic classes. We emphasize the scope and limitations of anthelmintics, antibiotics, antifungals, antivirals, antimalarials, antihypertensives, psychopharmaceuticals and antidiabetics that have shown extensive immunomodulatory, antiproliferative, pro-apoptotic, and antimetastatic potential. These drugs, either used alone or in combination with existing anticancer chemotherapeutics, represent strong candidates to prevent or overcome drug resistance. We particularly focus on outcomes and future perspectives of drug repositioning for the treatment of multidrug resistant tumors and discuss current possibilities and limitations of preclinical and clinical investigations.

Original languageEnglish
Article number100713
JournalDrug Resistance Updates
Volume52
DOIs
Publication statusPublished - Sep 2020

Keywords

  • Clinical cancer trials
  • Drug repurposing
  • Multidrug resistant cancer
  • Pharmacophore modelling
  • Virtual screening

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Cancer Research
  • Infectious Diseases
  • Pharmacology (medical)

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  • Cite this

    Dinić, J., Efferth, T., García-Sosa, A. T., Grahovac, J., Padrón, J. M., Pajeva, I., Rizzolio, F., Saponara, S., Spengler, G., & Tsakovska, I. (2020). Repurposing old drugs to fight multidrug resistant cancers. Drug Resistance Updates, 52, [100713]. https://doi.org/10.1016/j.drup.2020.100713