Repurposing old drugs to fight multidrug resistant cancers
García-Sosa, Alfonso T.
Padrón, José M.
Article (Published version)
© 2020 Elsevier Ltd
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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.
Keywords:Clinical cancer trials; Drug repurposing; Multidrug resistant cancer; Pharmacophore modelling; Virtual screening
Source:Drug Resistance Updates, 2020, 52, 100713-
- Ministry of Education, Science and Technological Development, Republic of Serbia, Grant no. 451-03-68/2020-14/200007 (University of Belgrade, Institute for Biological Research 'Siniša Stanković') (RS-200007)
- COST Action CA17104 STRATAGEM
- Deutsche Forschungsgemeinschaft
- Deutsche Krebshilfe
- Pharmacodynamic and pharmacogenomic research of new drugs in the treatment of solid tumors (RS-41026)
- Spanish Government for financial support through project PGC2018-094503-B-C22
- National Science Fund of Bulgaria (grant No. KP-06-COST/3/18.06.2019)
- Fondazione AIRC per la Ricerca sul Cancro (grant No. IG23566)