Hunt Sunny, Thyagarajan Anita, Sahu Ravi P
Department of Chemistry and Biochemistry, Oberlin College, 173 W Lorain St, Oberlin, OH 44074, USA.
Department of Pharmacology and Toxicology, Boonshoft School of Medicine, Dayton, OH 45435, USA.
Med Sci (Basel). 2025 Apr 23;13(2):47. doi: 10.3390/medsci13020047.
Cancer is the second leading cause of mortality worldwide. Despite the available treatment options, a majority of cancer patients develop drug resistance, indicating the need for alternative approaches. Repurposed drugs, such as antiglycolytic and anti-microbial agents, have gained substantial attention as potential alternative strategies against different disease pathophysiologies, including lung cancer. To that end, multiple studies have suggested that the antiglycolytic dichloroacetate (DCA) and the antibiotic salinomycin (SAL) possess promising anticarcinogenic activity, attributed to their abilities to target the key metabolic enzymes, ion transport, and oncogenic signaling pathways involved in regulating cancer cell behavior, including cell survival and proliferation. We used the following searches and selection criteria. (1) Biosis and PubMed were used with the search terms dichloroacetate; salinomycin; dichloroacetate as an anticancer agent; salinomycin as an anticancer agent; dichloroacetate side effects; salinomycin side effects; salinomycin combination therapy; dichloroacetate combination therapy; and dichloroacetate or salinomycin in combination with other agents, including chemotherapy and tyrosine kinase inhibitors. (2) The exclusion criteria included not being related to the mechanisms of DCA and SAL or not focusing on their anticancer properties. (3) All the literature was sourced from peer-reviewed journals within a timeframe of 1989 to 2024. Importantly, experimental studies have demonstrated that both DCA and SAL exert promising anticarcinogenic properties, as well as having synergistic effects in combination with other therapeutic agents, against multiple cancer models. The goal of this review is to highlight the mechanistic workings and efficacy of DCA and SAL as monotherapies, and their combination with other therapeutic agents in various cancer models, with a major emphasis on non-small-cell lung cancer (NSCLC) treatment.
癌症是全球第二大致死原因。尽管有多种治疗选择，但大多数癌症患者会产生耐药性，这表明需要采用替代方法。重新利用的药物，如抗糖酵解剂和抗菌剂，作为针对包括肺癌在内的不同疾病病理生理学的潜在替代策略，已受到广泛关注。为此，多项研究表明，抗糖酵解剂二氯乙酸（DCA）和抗生素沙利霉素（SAL）具有有前景的抗癌活性，这归因于它们能够靶向参与调节癌细胞行为（包括细胞存活和增殖）的关键代谢酶、离子转运和致癌信号通路。我们使用了以下检索和筛选标准。（1）在Biosis和PubMed中使用检索词二氯乙酸；沙利霉素；二氯乙酸作为抗癌剂；沙利霉素作为抗癌剂；二氯乙酸的副作用；沙利霉素的副作用；沙利霉素联合治疗；二氯乙酸联合治疗；以及二氯乙酸或沙利霉素与其他药物（包括化疗药物和酪氨酸激酶抑制剂）联合使用。（2）排除标准包括与DCA和SAL的作用机制无关或未聚焦于它们的抗癌特性。（3）所有文献均来自1989年至2024年期间的同行评审期刊。重要的是，实验研究表明，DCA和SAL都具有有前景的抗癌特性，并且与其他治疗药物联合使用时对多种癌症模型具有协同作用。本综述的目的是强调DCA和SAL作为单一疗法以及它们与其他治疗药物在各种癌症模型中的联合使用的作用机制和疗效，主要侧重于非小细胞肺癌（NSCLC）的治疗。
