Faculty of Pharmacy and Health Sciences, Royal College of Medicine Perak, Universiti Kuala Lumpur (RCMP UniKL), Ipoh, Perak, Malaysia; Respiratory Technology, Woolcock Institute of Medical Research, and Discipline of Pharmacology, Faculty of Medicine and Health, The University of Sydney, NSW 2037, Australia; Centre for Lung Cancer Research, 431 Glebe Point Road, 2037, Australia.
Faculty of Pharmacy and Health Sciences, Royal College of Medicine Perak, Universiti Kuala Lumpur (RCMP UniKL), Ipoh, Perak, Malaysia; Respiratory Technology, Woolcock Institute of Medical Research, and Discipline of Pharmacology, Faculty of Medicine and Health, The University of Sydney, NSW 2037, Australia; Centre for Lung Cancer Research, 431 Glebe Point Road, 2037, Australia.
Adv Drug Deliv Rev. 2018 Aug;133:107-130. doi: 10.1016/j.addr.2018.08.012. Epub 2018 Sep 4.
Lung cancer is a highly invasive and prevalent disease with ineffective first-line treatment and remains the leading cause of cancer death in men and women. Despite the improvements in diagnosis and therapy, the prognosis and outcome of lung cancer patients is still poor. This could be associated with the lack of effective first-line oncology drugs, formation of resistant tumors and non-optimal administration route. Therefore, the repurposing of existing drugs currently used for different indications and the introduction of a different method of drug administration could be investigated as an alternative to improve lung cancer therapy. This review describes the rationale and development of repositioning of drugs for lung cancer treatment with emphasis on inhalation. The review includes the current progress of repurposing non-cancer drugs, as well as current chemotherapeutics for lung malignancies via inhalation. Several potential non-cancer drugs such as statins, itraconazole and clarithromycin, that have demonstrated preclinical anti-cancer activity, are also presented. Furthermore, the potential challenges and limitations that might hamper the clinical translation of repurposed oncology drugs are described.
肺癌是一种侵袭性强、发病率高的疾病,一线治疗效果不佳,仍是男性和女性癌症死亡的主要原因。尽管在诊断和治疗方面有所改善,但肺癌患者的预后和结局仍然较差。这可能与缺乏有效的一线肿瘤药物、耐药肿瘤的形成以及非最佳给药途径有关。因此,重新利用目前用于不同适应症的现有药物,并引入不同的给药方法,可能是改善肺癌治疗的一种替代方法。本综述描述了重新定位药物治疗肺癌的原理和进展,重点介绍了吸入疗法。该综述包括重新定位非癌症药物以及通过吸入治疗肺癌的当前进展。还介绍了几种具有临床前抗癌活性的潜在非癌症药物,如他汀类药物、伊曲康唑和克拉霉素。此外,还描述了可能阻碍重新定位肿瘤药物临床转化的潜在挑战和限制。