Repurposing old drugs to fight multidrug resistant cancers
2020
Autori:
Dinić, JelenaEfferth, Thomas
García-Sosa, Alfonso T.
Grahovac, Jelena
Padrón, José M.
Pajeva, Ilza
Rizzolio, Flavio
Saponara, Simona
Spengler, Gabriella
Tsakovska, Ivanka
Tip dokumenta:
Članak u časopisu (Objavljena verzija)
,
© 2020 Elsevier Ltd
Metapodaci
Prikaz svih podataka o dokumentuApstrakt:
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.
Ključne reči:
Clinical cancer trials; Drug repurposing; Multidrug resistant cancer; Pharmacophore modelling; Virtual screeningIzvor:
Drug Resistance Updates, 2020, 52, 100713-Finansiranje / projekti:
- Ministarstvo nauke, tehnološkog razvoja i inovacija Republike Srbije, institucionalno finansiranje - 200007 (Univerzitet u Beogradu, Institut za biološka istraživanja 'Siniša Stanković') (RS-MESTD-inst-2020-200007)
- COST Action CA17104 STRATAGEM
- Deutsche Forschungsgemeinschaft
- Deutsche Krebshilfe
- Farmakodinamska i farmakogenomska ispitivanja novijih lekova u lečenju solidnih tumora (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-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)
DOI: 10.1016/j.drup.2020.100713
ISSN: 1368-7646
PubMed: 32615525