Repurposed anti-cancer drugs: the future for anti-infective therapy?

Quezada, Héctor; Martínez‐Vázquez, Mariano; López-Jácome, Esaú; González‐Pedrajo, Bertha; Andrade, Ángel; Fernández-Presas, Ana María; Tovar-García, Arturo; García‐Contreras, Rodolfo

doi:10.1080/14787210.2020.1752665

Cited by 27 publications

(20 citation statements)

References 31 publications

(38 reference statements)

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“…However, administration of anticancer molecules to patients who are often immunocompromised should only be taken after careful consideration due to the numerous side effects that these compounds can cause, including immunosuppression [90]. A bypass solution via a synergistic association could circumvent this limitation.…”

Section: Anticancer Drugsmentioning

confidence: 99%

Drug Repurposing in Medical Mycology: Identification of Compounds as Potential Antifungals to Overcome the Emergence of Multidrug-Resistant Fungi

et al. 2021

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Immunodepression, whether due to HIV infection or organ transplantation, has increased human vulnerability to fungal infections. These conditions have created an optimal environment for the emergence of opportunistic infections, which is concomitant to the increase in antifungal resistance. The use of conventional antifungal drugs as azoles and polyenes can lead to clinical failure, particularly in immunocompromised individuals. Difficulties related to treating fungal infections combined with the time required to develop new drugs, require urgent consideration of other therapeutic alternatives. Drug repurposing is one of the most promising and rapid solutions that the scientific and medical community can turn to, with low costs and safety advantages. To treat life-threatening resistant fungal infections, drug repurposing has led to the consideration of well-known and potential molecules as a last-line therapy. The aim of this review is to provide a summary of current antifungal compounds and their main resistance mechanisms, following by an overview of the antifungal activity of non-traditional antimicrobial drugs. We provide their eventual mechanisms of action and the synergistic combinations that improve the activity of current antifungal treatments. Finally, we discuss drug repurposing for the main emerging multidrug resistant (MDR) fungus, including the Candida auris, Aspergillus or Cryptococcus species.

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Section: Anticancer Drugsmentioning

confidence: 99%

Drug Repurposing in Medical Mycology: Identification of Compounds as Potential Antifungals to Overcome the Emergence of Multidrug-Resistant Fungi

et al. 2021

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“…Repositioning studies of anti-cancer drugs has led to the discovery that targeting certain host proteins yields broad-spectrum anti-infective activity, a further contribution away from the magic bullet paradigm 77 . Heat shock protein 90 (Hsp90) inhibitors and oestrogen receptor antagonists have unearthed therapeutic targets whose modulation may successfully treat malignancies as well as infection.…”

Section: Anti-cancer Drugs As Broad-spectrum Anti-infectivesmentioning

confidence: 99%

A New Determination of Pan-Pathogen Antimicrobials

Prathapan

2021

Preprint

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Drug repositioning studies in recent decades have revealed a growing number of antimicrobials effective at treating infection types tangential to their original antimicrobial classification. Such ‘pan-pathogen antimicrobials’ (or ‘broad-spectrum anti-infectives’) have not yet been formally characterised. This review examines historical limitations of the canonical antimicrobial lexicon in light of the contemporary model for infectious disease and propounds a taxonomy that defines antimicrobials according to the host-pathogen interactome, not the pathogen. By doing so, antimicrobials that are effective at treating multiple infection types are highlighted, namely azithromycin, ivermectin, niclosamide, and nitazoxanide. Recognition of the pan-pathogen nature of these antimicrobials can stimulate a more unified approach to antimicrobial development cognisant of generalised anti-infective mechanisms within the host-pathogen interactome and anticipatory of future pandemics and bioterrorist attacks.

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“…For instance, Celecoxib ( 2 ) and related NSAIDs were found to increase the efficacy of cisplatin, paclitaxel, and doxorubicin against human cervical cancer ( 3 ). In addition, some anti-cancer drugs have been successfully used as efficient anti-bacterial agents ( 4 ), and as reviewed here, nucleoside/nucleotide analogues, have been repurposed as anti-cancer agents.…”

Section: Introductionmentioning

confidence: 99%

Putative Repurposing of Lamivudine, a Nucleoside/Nucleotide Analogue and Antiretroviral to Improve the Outcome of Cancer and COVID-19 Patients

2021

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Lamivudine, also widely known as 3TC belongs to a family of nucleotide/nucleoside analogues of cytidine or cytosine that inhibits the Reverse Transcriptase (RT) of retroviruses such as HIV. Lamivudine is currently indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection or for chronic Hepatitis B (HBV) virus infection associated with evidence of hepatitis B viral replication and active liver inflammation. HBV reactivation in patients with HBV infections who receive anticancer chemotherapy can be a life-threatening complication during and after the completion of chemotherapy. Lamivudine is used, as well as other antiretrovirals, to prevent the reactivation of the Hepatitis B virus during and after chemotherapy. In addition, Lamivudine has been shown to sensitize cancer cells to chemotherapy. Lamivudine and other similar analogues also have direct positive effects in the prevention of cancer in hepatitis B or HIV positive patients, independently of chemotherapy or radiotherapy. Recently, it has been proposed that Lamivudine might be also repurposed against SARS-CoV-2 in the context of the COVID-19 pandemic. In this review we first examine recent reports on the re-usage of Lamivudine or 3TC against the SARS-CoV-2, and we present docking evidence carried out in silico suggesting that Lamivudine may bind and possibly work as an inhibitor of the SARS-CoV-2 RdRp RNA polymerase. We also evaluate and propose assessment of repurposing Lamivudine as anti-SARS-CoV-2 and anti-COVID-19 antiviral. Secondly, we summarize the published literature on the use of Lamivudine or (3TC) before or during chemotherapy to prevent reactivation of HBV, and examine reports of enhanced effectiveness of radiotherapy in combination with Lamivudine treatment against the cancerous cells or tissues. We show that the anti-cancer properties of Lamivudine are well established, whereas its putative anti-COVID effect is under investigation. The side effects of lamivudine and the appearance of resistance to 3TC are also discussed.

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Repurposed anti-cancer drugs: the future for anti-infective therapy?

Cited by 27 publications

References 31 publications

Drug Repurposing in Medical Mycology: Identification of Compounds as Potential Antifungals to Overcome the Emergence of Multidrug-Resistant Fungi

Drug Repurposing in Medical Mycology: Identification of Compounds as Potential Antifungals to Overcome the Emergence of Multidrug-Resistant Fungi

A New Determination of Pan-Pathogen Antimicrobials

Putative Repurposing of Lamivudine, a Nucleoside/Nucleotide Analogue and Antiretroviral to Improve the Outcome of Cancer and COVID-19 Patients

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