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In this work, we conducted a review on the antitumor mechanisms of aminoquinolines, focusing on the responses and differences of tumor histological tissues and toxicity related to pharmacokinetics. This well-defined analysis shows similar mechanistic forms triggered by aminoquinolines in different histological tumor tissues and under coexposure conditions, although different pharmacological potencies also occur. These molecules are lysosomotropic amines that increase the antiproliferative action of chemotherapeutic agents, mainly by cell cycle arrest, histone acetylation, physiological changes in tyrosine kinase metabolism, inhibition of PI3K\/Akt\/mTOR pathways, cyclin D1, E2F1, angiogenesis, ribosome biogenesis, triggering of ATM-ATR\/p53\/p21 signaling, apoptosis, and presentation of tumor peptides. Their chemo\/radiotherapy sensitization effects may be an adjuvant option against solid tumors, since 4-aminoquinolines induce lysosomal-mediated programmed cytotoxicity of cancer cells and accumulation of key markers, predominantly, LAMP1, p62\/SQSTM1, LC3 members, GAPDH, beclin-1\/Atg6, \u03b1-synuclein, and granules of lipofuscin. Adverse effects are dose-dependent, though most common with chloroquine, hydroxychloroquine, amodiaquine, and other aminoquinolines are gastrointestinal changes, blurred vision ventricular arrhythmias, cardiac arrest, QTc prolongation, severe hypoglycemia with loss of consciousness, and retinopathy, and they are more common with chloroquine than with hydroxychloroquine and amodiaquine due to pharmacokinetic features. Additionally, psychological\/neurological effects were also detected during acute or chronic use, but aminoquinolines do not cross the placenta easily and low quantity is found in breast milk despite their long mean residence times, which depends on the coexistence of hepatic diseases (cancer-related or not), first pass metabolism, and comedications. The low cost and availability on the world market have converted aminoquinolines into \u201cstar drugs\u201d for pharmaceutical repurposing, but a continuous pharmacovigilance is necessary because these antimalarials have multiple modes of action\/unwanted targets, relatively narrow therapeutic windows, recurrent adverse effects, and related poisoning self-treatment. Therefore, their use must obey strict rules, ethical and medical prescriptions, and clinical and laboratory monitoring.<\/jats:p>","DOI":"10.1155\/2021\/3569349","type":"journal-article","created":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T23:50:26Z","timestamp":1630972226000},"page":"1-18","source":"Crossref","is-referenced-by-count":15,"title":["Aminoquinolines as Translational Models for Drug Repurposing: Anticancer Adjuvant Properties and Toxicokinetic-Related Features"],"prefix":"10.1155","volume":"2021","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6862-6497","authenticated-orcid":true,"given":"Paulo Michel Pinheiro","family":"Ferreira","sequence":"first","affiliation":[{"name":"Department of Biophysics and Physiology, Laboratory of Experimental Cancerology (LabCancer), Federal University of Piau\u00ed, Teresina 64049-550, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1503-9528","authenticated-orcid":true,"given":"Jos\u00e9 Roberto de Oliveira","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Center for Integrative Sciences, State University of Health Sciences of Alagoas, Macei\u00f3 57010-382, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7033-9198","authenticated-orcid":true,"given":"Rayran Walter Ramos de","family":"Sousa","sequence":"additional","affiliation":[{"name":"Department of Biophysics and Physiology, Laboratory of Experimental Cancerology (LabCancer), Federal University of Piau\u00ed, Teresina 64049-550, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6774-2063","authenticated-orcid":true,"given":"Daniel Pereira","family":"Bezerra","sequence":"additional","affiliation":[{"name":"Gon\u00e7alo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ-BA), Salvador 40296-710, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7865-5002","authenticated-orcid":true,"given":"Gardenia Carmen Gadelha","family":"Milit\u00e3o","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Federal University of Pernambuco, Recife 50670-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(16)30143-7"},{"key":"2","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1016\/S0140-6736(16)31679-8","article-title":"Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990\u20132015: a systematic analysis for the global burden of disease study 2015","volume":"388","author":"GBD Risk Factors Collaborators","year":"2016","journal-title":"The Lancet"},{"key":"3","volume-title":"Cancer. 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