Drug Repurposing to Target the Apoptosome in MAPKi-Resistant Melanoma

Carotenuto, Pietro; Romano, Alessia; Barbato, Anna; Quadrano, Paola; Brillante, Simona; Volpe, Mariagrazia; Ferrante, Luigi; Tammaro, Roberta; Morleo, Manuela; Cegli, Rossella De; Iuliano, Antonella; Ciliberto, Gennaro; Clery, Eduardo; Troncone, Giancarlo; Palma, Giuseppe; Arra, Claudio; Barbieri, Antônio; Capone, Marieelena; Madonna, Gabriele; Ascierto, Paolo A.; Lanfrancone, Luisa; Indrieri, Alessia; Bazzoli, Franco

doi:10.2139/ssrn.3883637

Cited by 1 publication

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“…Another study pointed out the restoration of sensitivity by QC through simultaneous upregulation of cathepsin L and downregulation of p62 sequestosome apparatus [55]. A few more studies have also reported the reversal of resistance to other chemotherapeutic drugs, including cytarabine in ALL xenografts, MAPK pathway inhibitors in NRAS and BRAF mutant melanoma, TRAIL in glioblastoma and hepatocellular carcinoma cells mostly through simultaneous downregulation of p62 and NF-κB, upregulation of p53, mitochondrial damage, and subsequent activation of caspases [54,85,91,92]. In addition to its aforementioned effects, QC has also been reported as an inhibitor of P-glycoproteins, thereby impairing its own efflux, as well as the combinational therapeutic administered with it [93,94].…”

Section: Quinacrine and Chemoresistancementioning

confidence: 99%

Repurposing of Anti-Malarial Drug Quinacrine for Cancer Treatment: A Review

Kumar¹,

Sarkar²

2022

Sci. Pharm.

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Quinacrine (QC), a synthetic drug belonging to the 9-aminoacridine family, has been used extensively to treat malaria and multiple ailments over the past several decades. Following its discovery in the 1920s and extensive use for the treatment of malaria for nearly two decades, numerous studies have explored its antineoplastic potential in both preclinical and clinical settings. Multiple studies spanning over seven decades have examined a wide range of QC anticancer activities across various types of cancers, along with the underlying mechanisms. Many of these mechanisms, including activation of the p53 signaling cascade and simultaneous NF-κB signaling inhibition, have been reported in various studies, bringing QC to a unique polypharmacological category drug possessing the potential to treat a wide variety of diseases, including cancer. This article summarizes most of the research conducted over several decades to uncover new molecular mechanisms activated or inactivated and directly correlate with antineoplastic activity QC.

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