Аннотация
New lights Through Old Windows: Metformin and Derivatives as Anti-Cancer TreatmentsThe current theme issue is intended to focus on the advances and the development of drug repurposing and strategies for cancer treatment.The issue contains the contributions from researchers studying various aspects of drug repurposing and screening for anticancer management with a particular interest in metformin (dimethylbiguanide) as well as other small marketed drugs.Metformin is the recommended first line of treatment of type 2 Diabetes Mellitus.Recently, metformin is gaining international interest for its potential use to treat/prevent different types of cancer, cardiovascular disease, ageing, and neurological disorders.Several studies reported the potential anticancer activity of metformin that promoted the initiation of tens of clinical trials that aimed to investigate its potential against endometrial, prostate, pancreas, lung and breast cancer.Nonetheless, uncertainties still exist with respect to understanding the cellular mode of action of metformin, its antiproliferative ability as well as the effective antiproliferative concentration.In their article "Metformin Adjunct With Antineoplastic Agents for the Treatment of Lung Cancer: A Meta-Analysis of Randomized Controlled Trials and Observational Cohort Studies" (Luo et al.) that evaluated the scientific literature on the efficacy of the combinational use of metformin and anticancer agents on lung cancer survival in both diabetic and non-diabetic patients. Briefly, the study is a comprehensive meta-analyses of randomized controlled trials (RCTs) and observational cohort studies with two outcome indicators, namely overall survival (OS) and progression-free survival (PFS). The clinical evidence obtained from the current analysis suggested that metformin, in combination with antineoplastic agents, may improve the PFS and OS compared to standard antineoplastic agents alone. While this finding is in line with our previously published work that metformin may provide synergistic effect to chemotherapy (Aljofan and Riethmacher, 2019), a number of studies suggested that metformin could be used, on its own, as a monotherapy for the management of cancer (Amaral et al., 2018;He et al., 2018;Mallik and Chowdhury, 2018;Tan et al., 2018). Though, the precise anticancer mechanism of metformin remains undetermined, a number of potential mechanisms were reported with the majority revolving around the activation of AMPactivated protein kinase (AMPK) pathway (Aljofan and Riethmacher, 2019), such as the induction of autophagy as a result of inhibition of mammalian target of rapamycin as a result of AMPKactivation (Luo et al.).Interestingly, another study in this theme titled "The Disulfiram/Copper Complex Induces Autophagic Cell Death in Colorectal Cancer by Targeting ULK1" (Hu et al.) claimed that disulfiram complexed with Copper (DSF/Cu) has a potential in the treatment of colorectal cancer.The study claimed that DSF/Cu inhibits cell viability of colorectal cancer cells in a dose dependent manner both in vitro and in vivo (subcutaneous xenograft mice model).The authors suggested that the DSF/Cu complex induced inhibition of cell viability was due to cellular