肺癌对全球公共健康造成了重大的死亡风险负担。由于这种癌症的隐匿性，不可避免地会出现诊断延迟，从而导致肿瘤的长期发展。非小细胞肺癌（NSCLC）占所有肺癌病例的80-85％，使得这种肿瘤形式成为肺癌的一种常见亚型。精确的非小细胞肺癌分类是正确诊断、预后和适当治疗的关键方面之一，其中基于生物标志物表达谱的方法尤为重要。这种生物标志物谱分析为患者分层、机制洞察和潜在药物靶点提供了机会。然而，大量患者出现了多种毒副作用、肿瘤复发和基于治疗的耐药性的发展。由于这些严峻情况的存在，我们迫切需要高效、有效的新型抗癌治疗方法。全新药物开发方法既昂贵又耗时，并且存在较高的退化率，其中部分原因是由于与毒性相关的问题。然而，药物重定位结合计算机辅助系统生物学方法则提供了发现新型高效和安全药物的替代方案。因此，在本综述中，我们将重点比较传统基于治疗的耐药机制与来自三个不同类别（抗寄生虫药物，抗抑郁药物和抗精神病药物）的重定位抗癌药物在非小细胞肺癌治疗中的应用。明确地，将这些新型治疗方法与传统的药物方案相结合，可能会互补/增强现有的治疗模式。这种方法具有重大的转化意义，因为它可以对抗药物耐药性和细胞毒性副作用，并为非小细胞肺癌患者提供一个相对新的治疗策略。© 2023. 作者，授予Springer Science+Business Media, LLC的独家许可，隶属于Springer Nature。

Globally, lung cancer contributes significantly to the public health burden-associated mortality. As this form of cancer is insidious in nature, there is an inevitable diagnostic delay leading to chronic tumor development. Non-small cell lung cancer (NSCLC) constitutes 80-85% of all lung cancer cases, making this neoplasia form a prevalent subset of lung carcinoma. One of the most vital aspects for proper diagnosis, prognosis, and adequate therapy is the precise classification of non-small cell lung cancer based on biomarker expression profiling. This form of biomarker profiling has provided opportunities for improvements in patient stratification, mechanistic insights, and probable druggable targets. However, numerous patients have exhibited numerous toxic side effects, tumor relapse, and development of therapy-based chemoresistance. As a result of these exacting situations, there is a dire need for efficient and effective new cancer therapeutics. De novo drug development approach is a costly and tedious endeavor, with an increased attrition rate, attributed, in part, to toxicity-related issues. Drug repurposing, on the other hand, when combined with computer-assisted systems biology approach, provides alternatives to the discovery of new, efficacious, and safe drugs. Therefore, in this review, we focus on a comparison of the conventional therapy-based chemoresistance mechanisms with the repurposed anti-cancer drugs from three different classes-anti-parasitic, anti-depressants, and anti-psychotics for cancer treatment with a primary focus on NSCLC therapeutics. Certainly, amalgamating these novel therapeutic approaches with that of the conventional drug regimen in NSCLC-affected patients will possibly complement/synergize the existing therapeutic modalities. This approach has tremendous translational significance, since it can combat drug resistance and cytotoxicity-based side effects and provides a relatively new strategy for possible application in therapy of individuals with NSCLC.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.