Cancer,ranging from early stages to metastatic spread,is one of the leading causes of death globally.Current treatment options,including chemotherapy,radiotherapy,and targeted drugs,have limitations substantial advers...Cancer,ranging from early stages to metastatic spread,is one of the leading causes of death globally.Current treatment options,including chemotherapy,radiotherapy,and targeted drugs,have limitations substantial adverse effects,the development of drug resistance,and high cost.To address these challenges,numerous studies have focused on repurposing existing drugs for anticancer therapy,with clotrimazole(CLZ)emerging as a promising candidate due to its notable anticancer activity.CLZ was first developed as an antifungal agent.Recently,significant anticancer effects have been observed making it a suitable candidate for drug repurposing.Compared with other azole-based antifungals,CLZ has shown distinct therapeutic effects on cancer cells via several pathways.Its ability to disrupt glycolysis by inhibiting phosphofructokinase(PFK)and hexokinase(HK)distinguishes it from other azoles.Furthermore,CLZ obstructs calcium homeostasis and critical survival pathways,such as extracellular signal-regulated kinase(ERK)-p65,phosphatidylinositol 3-kinase(PI3K),and mitochondrial apoptotic pathways,inhibiting tumor growth,inducing apoptosis,and attenuating metastasis.This review summarizes the potential of CLZ repurposing for cancer therapy,emphasizing its well-established safety profile and cost-effectiveness while addressing unmet clinical needs in current cancer treatment.It briefly examines in vitro and in vivo assessments to understand the mechanisms and effects of CLZ on various cancer types.Furthermore,novel strategies such as nanoformulations and combination therapies with existing chemotherapeutic drugs have been highlighted to improve therapeutic outcomes.Preclinical studies have provided promising evidence for the efficacy of CLZ in different cancers,showing tumor regression and improved responses to conventional chemotherapy or targeted therapies.Given its evident preclinical results and diverse mechanisms of action,CLZ may be considered an antineoplastic agent.Further clinical research is required to fully elucidate its anticancer potential,potentially positing it as a valuable addition to currently available cancer treatments.展开更多
文摘Cancer,ranging from early stages to metastatic spread,is one of the leading causes of death globally.Current treatment options,including chemotherapy,radiotherapy,and targeted drugs,have limitations substantial adverse effects,the development of drug resistance,and high cost.To address these challenges,numerous studies have focused on repurposing existing drugs for anticancer therapy,with clotrimazole(CLZ)emerging as a promising candidate due to its notable anticancer activity.CLZ was first developed as an antifungal agent.Recently,significant anticancer effects have been observed making it a suitable candidate for drug repurposing.Compared with other azole-based antifungals,CLZ has shown distinct therapeutic effects on cancer cells via several pathways.Its ability to disrupt glycolysis by inhibiting phosphofructokinase(PFK)and hexokinase(HK)distinguishes it from other azoles.Furthermore,CLZ obstructs calcium homeostasis and critical survival pathways,such as extracellular signal-regulated kinase(ERK)-p65,phosphatidylinositol 3-kinase(PI3K),and mitochondrial apoptotic pathways,inhibiting tumor growth,inducing apoptosis,and attenuating metastasis.This review summarizes the potential of CLZ repurposing for cancer therapy,emphasizing its well-established safety profile and cost-effectiveness while addressing unmet clinical needs in current cancer treatment.It briefly examines in vitro and in vivo assessments to understand the mechanisms and effects of CLZ on various cancer types.Furthermore,novel strategies such as nanoformulations and combination therapies with existing chemotherapeutic drugs have been highlighted to improve therapeutic outcomes.Preclinical studies have provided promising evidence for the efficacy of CLZ in different cancers,showing tumor regression and improved responses to conventional chemotherapy or targeted therapies.Given its evident preclinical results and diverse mechanisms of action,CLZ may be considered an antineoplastic agent.Further clinical research is required to fully elucidate its anticancer potential,potentially positing it as a valuable addition to currently available cancer treatments.
