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This review discusses repurposable drugs that target NSCLC’s inflammatory tumor microenvironment, emphasizing inflammation-driven DNA damage, enhanced cell division, and airway delivery, including physicochemical and nanocarrier 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\nThiviyadarshini Rajasegaran 1, Chee Wun How 2, Anoosha Saud 1, Azhar Ali 3,† and Jonathan Chee Woei Lim 1, *,†  \nCitation: Rajasegaran, T.; How, C.W.; Saud, A.; Ali, A.; Lim, J.C.W. Targeting Inflammation in Non-Small Cell Lung Cancer through Drug Repurposing. Pharmaceuticals 2023, 16, 451. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)ph16030451  \nAcademic Editor: Barbara Ruaro  \nReceived: 13 February 2023  \nRevised: 12 March 2023  \nAccepted: 14 March 2023  \nPublished: 16 March 2023  \nCopyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Department of Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang`43400, Selangor, Malaysia  \n2 School of Pharmacy, Monash University Malaysia, Bandar Sunway, Subang Jaya 47500, Selangor, Malaysia  \n3 Cancer Science Institute Singapore, National University of Singapore, Singapore 117599, Singapore  \n* Correspondence: [cheewoei@upm.edu.my](cheewoei@upm.edu.my)[ ](cheewoei@upm.edu.my)† These authors contributed equally to this work.  \nAbstract: Lung cancer is the most common cause of cancer-related deaths. Lung cancers can beclassified as small-cell (SCLC) or non-small cell (NSCLC) . About 84% of all lung cancers are NSCLC and about 16% are SCLC. For the past few years, there have been a lot of new advances in the management of NSCLC in terms of screening, diagnosis and treatment. Unfortunately, most of the NSCLCs are resistant to current treatments and eventually progress to advanced stages. In this perspective, we discuss some of the drugs that can be repurposed to specifically target the inflammatory pathway of NSCLC utilizing its well-defined inflammatory tumor microenvironment. Continuous inflammatory conditions are responsible to induce DNA damage and enhance cell division rate in lung tissues. There are existing anti-inflammatory drugs which were found suitable for repurposing in non-small cell lung carcinoma (NSCLC) treatment and drug modification for delivery via inhalation. Repurposing anti-inflammatory drugs and their delivery through the airway is a promising strategy to treat NSCLC. In this review, suitable drug candidates that can be repurposed to treat inflammation-mediated NSCLC will be comprehensively discussed together with their administration via inhalation from physico-chemical and nanocarrier perspectives.  \nKeywords: non-small cell lung cancer; inflammation; drug-repurposing; inhalation; drug delivery  \n1. Introduction  \nAccording to GLOBOCAN 2020, lung cancer tops the cancer list, with highest fatality rate and accounts for 18% of all cancer deaths worldwide [1] . About 84% of lung cancer cases belongs to non-small cell lung carcinoma (NSCLC) and the remaining 15% belongs to small cell lung carcinoma (SCLC) [2] . NSCLC is categorized into three sub-types: adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. Adenocarcinoma is the major subtype with about 45% of all NSCLC followed by squamous cell carcinoma with 25–30% and the remaining 5–10% is large cell carcinoma subtype [3] . Late diagnosis of disease (at stage III and IV) is the major factor for the poor survival rate in lung cancer patients as the disease has progressed to the metastatic stage. About 92% of patients diagnosed at stage IA1 could survived for 5 years or more compared to 10% of patients diagnosed at stage IV. Furthermore, slight enlargement in tumor size from \u003C1 cm (stage IA1) to >2 cm (stage IA3) could reduce the 5-year survival rate of patients from 92% to 77%[4] .  \nCurrent NCSLC therapies, including surgery, chemotherapy, a","cbCaiqa5rXPSKXJs","https://ap.wps.com/l/cbCaiqa5rXPSKXJs","pdf",2263146,"English","# Abstract\n# Introduction\n## Epidemiology and subtypes of lung cancer\n## Limitations of current NSCLC therapies\n## Current targeted therapies and resistance\n## Immunotherapy in NSCLC","[{\"question\":\"Why does inflammation play a key role in NSCLC progression?\",\"answer\":\"Continuous inflammatory conditions can induce DNA damage and increase the cell division rate in lung tissues, supporting tumor progression.\"},{\"question\":\"What makes current NSCLC treatments insufficient?\",\"answer\":\"Surgery, chemotherapy, and radiotherapy often lack precision, suffer from low drug bioavailability due to first-pass metabolism, and cause serious adverse effects from non-specific targeting.\"},{\"question\":\"How does the review propose repurposed anti-inflammatory drugs could be delivered to NSCLC?\",\"answer\":\"It highlights repurposing anti-inflammatory drugs and delivering them through the airway, discussing candidate drugs from both physicochemical and nanocarrier perspectives.\"}]","Targeting Inflammation in Non-Small Cell Lung Cancer through Drug Repurposing | PDF",1790270334,76]