Editorial

4 pages, 192 KiB

Open AccessEditorial

Advances in Non-Small Cell Lung Cancer (NSCLC) Treatment—A Paradigm Shift in Oncology

by Azhar Ali

Pharmaceuticals 2024, 17(2), 246; https://doi.org/10.3390/ph17020246 - 13 Feb 2024

Viewed by 968

Non-Small Cell Lung Cancer (NSCLC) management remains a formidable challenge in the field of oncology, representing a significant global health burden [...] Full article

(This article belongs to the Special Issue Advances in Non-small Cell Lung Cancer Treatment - Current and Future)

Research

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11 pages, 4444 KiB

Open AccessCommunication

Prognostic Value of CXCL12 in Non-Small Cell Lung Cancer Patients Undergoing Tumor Resection

by Yurie Kogue, Hiroyasu Kobayashi, Yutaka Nakamura, Takatsugu Takano, Chihiro Furuta, Osamu Kawano, Taro Yasuma, Tadashi Nishimura, Corina N. D’Alessandro-Gabazza, Hajime Fujimoto, Esteban C. Gabazza, Tetsu Kobayashi and Ichiro Fukai

Pharmaceuticals 2023, 16(2), 255; https://doi.org/10.3390/ph16020255 - 07 Feb 2023

Cited by 2 | Viewed by 1359

Abstract

Adjuvant chemotherapy is commonly indicated in lung cancer patients undergoing surgical therapy because tumor recurrence is frequent. A biomarker that can predict tumor recurrence in the postoperative period is currently unavailable. CXCR4 receptor and its ligand CXCL12 play important roles in metastasis. This [...] Read more.

Adjuvant chemotherapy is commonly indicated in lung cancer patients undergoing surgical therapy because tumor recurrence is frequent. A biomarker that can predict tumor recurrence in the postoperative period is currently unavailable. CXCR4 receptor and its ligand CXCL12 play important roles in metastasis. This study investigated the value of tumor CXCL12 expression to predict prognosis and indicate adjuvant chemotherapy in non-small cell lung cancer patients. This study enrolled 82 non-small cell lung cancer patients. The expression of CXCL12 was evaluated by immunohistochemistry. The degree of CXCL12 expression was assessed using the Allred score system. Among all subjects, the progression-free survival and overall survival were significantly prolonged in cancer patients with low tumor expression of CXCL12 compared to patients with high tumor expression. Multivariate analysis showed that the increased level of CXCL12 is a significant predictor of progression-free survival and overall survival in NSCLC patients. Among subjects with high tumor CXCL12 expression, progression-free survival and overall survival were significantly improved in patients treated with adjuvant chemotherapy compared to untreated patients. These results suggest the potential value of tumor CXCL12 expression as a marker to predict prognosis and to indicate adjuvant chemotherapy after surgical tumor resection in non-small cell lung cancer patients. Full article

(This article belongs to the Special Issue Advances in Non-small Cell Lung Cancer Treatment - Current and Future)

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14 pages, 3358 KiB

Open AccessArticle

Sorafenib Alleviates Inflammatory Signaling of Tumor Microenvironment in Precancerous Lung Injuries

by Betul Cicek, Ahmet Hacimuftuoglu, Mehmet Kuzucu, Ahmet Cetin, Yesim Yeni, Sidika Genc, Serkan Yildirim, Ismail Bolat, Mecit Kantarci, Mustafa Gul, Serhat Hayme, Dimitris Matthaios, Dimitra P. Vageli, Sotirios G. Doukas, Aristidis Tsatsakis and Ali Taghizadehghalehjoughi

Pharmaceuticals 2023, 16(2), 221; https://doi.org/10.3390/ph16020221 - 01 Feb 2023

Cited by 3 | Viewed by 2074

Abstract

According to population-based studies, lung cancer is the prominent reason for cancer-related mortality worldwide in males and is also rising in females at an alarming rate. Sorafenib (SOR), which is approved for the treatment of hepatocellular carcinoma and renal cell carcinoma, is a [...] Read more.

According to population-based studies, lung cancer is the prominent reason for cancer-related mortality worldwide in males and is also rising in females at an alarming rate. Sorafenib (SOR), which is approved for the treatment of hepatocellular carcinoma and renal cell carcinoma, is a multitargeted protein kinase inhibitor. Additionally, SOR is the subject of interest for preclinical and clinical trials in lung cancer. This study was designed to assess in vivo the possible effects of sorafenib (SOR) in diethylnitrosamine (DEN)-induced lung carcinogenesis and examine its probable mechanisms of action. A total of 30 adult male rats were divided into three groups (1) control, (2) DEN, and (3) DEN + SOR. The chemical induction of lung carcinogenesis was performed by injection of DEN intraperitoneally at 150 mg/kg once a week for two weeks. The DEN-administered rats were co-treated with SOR of 10 mg/kg by oral gavage for 42 alternate days. Serum and lung tissue samples were analyzed to determine SRY-box transcription factor 2 (SOX-2) levels. The tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) levels were measured in lung tissue supernatants. Lung sections were analyzed for cyclooxygenase-2 (COX-2) and c-Jun N-terminal kinase (JNK) histopathologically. In addition, cyclooxygenase-2 (COX-2) and c-Jun N-terminal kinase (JNK) were analyzed by immunohistochemistry and immunofluorescence methods, respectively. SOR reduced the level of SOX-2 that maintenance of cancer stemness and tumorigenicity, and TNF-α and IL-1β levels. Histopathological analysis demonstrated widespread inflammatory cell infiltration, disorganized alveolar structure, hyperemia in the vessels, and thickened alveolar walls in DEN-induced rats. The damage was markedly reduced upon SOR treatment. Further, immunohistochemical and immunofluorescence analysis also revealed increased expression of COX-2 and JNK expression in DEN-intoxicated rats. However, SOR treatment alleviated the expression of these inflammatory markers in DEN-induced lung carcinogenesis. These findings suggested that SOR inhibits DEN-induced lung precancerous lesions through decreased inflammation with concomitant in reduced SOX-2 levels, which enables the maintenance of cancer stem cell properties. Full article

(This article belongs to the Special Issue Advances in Non-small Cell Lung Cancer Treatment - Current and Future)

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10 pages, 1505 KiB

Open AccessArticle

Pembrolizumab and Chemotherapy Combination Prolonged Progression-Free Survival in Patients with NSCLC with High PD-L1 Expression and Low Neutrophil-to-Lymphocyte Ratio

by Jeng-Shiuan Tsai, Sheng-Huan Wei, Chian-Wei Chen, Szu-Chun Yang, Yau-Lin Tseng, Po-Lan Su, Chien-Chung Lin and Wu-Chou Su

Pharmaceuticals 2022, 15(11), 1407; https://doi.org/10.3390/ph15111407 - 14 Nov 2022

Cited by 4 | Viewed by 1829

Abstract

The use of immune checkpoint inhibitors (ICIs) has provided overall survival (OS) benefits in patients with treatment-naïve advanced non-small cell lung cancer (NSCLC) without targetable driver mutations. However, studies comparing ICIs monotherapy with combination therapy either with chemotherapy or radiotherapy in programmed death-ligand [...] Read more.

The use of immune checkpoint inhibitors (ICIs) has provided overall survival (OS) benefits in patients with treatment-naïve advanced non-small cell lung cancer (NSCLC) without targetable driver mutations. However, studies comparing ICIs monotherapy with combination therapy either with chemotherapy or radiotherapy in programmed death-ligand 1 high expressors remain limited. This study aimed to retrospectively compare the treatment efficacy of the therapies by studying 47 patients with treatment-naïve advanced NSCLC who received ICI monotherapy (n = 28) or combination therapy either with chemotherapy or radiotherapy (n = 19). Progression-free survival (PFS) and OS were estimated using the Kaplan–Meier method and compared using log–rank tests. It was observed that patients who received combination therapy had a better PFS than monotherapy, but no such significant benefit was observed in OS. The difference in PFS was higher in the subgroup of patients with low neutrophil-to-lymphocyte ratio (NLR) than in the high-NLR patient subgroup. This study suggests that pembrolizumab in combination with chemotherapy or radiotherapy could provide a significant benefit in PFS, especially in patients with treatment-naïve advanced NSCLC with low NLR. Furthermore, our study also demonstrates the potential use of NLR as a biomarker for prediction of treatment outcomes in patients with advanced NSCLC receiving combination therapy. Full article

(This article belongs to the Special Issue Advances in Non-small Cell Lung Cancer Treatment - Current and Future)

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14 pages, 1573 KiB

Open AccessArticle

Real-World Analysis of Nivolumab and Atezolizumab Efficacy in Previously Treated Patients with Advanced Non-Small Cell Lung Cancer

by Miriam Alonso-García, Amparo Sánchez-Gastaldo, Miguel A. Muñoz-Fuentes, Sonia Molina-Pinelo, Laura Boyero, Johana Cristina Benedetti and Reyes Bernabé-Caro

Pharmaceuticals 2022, 15(5), 533; https://doi.org/10.3390/ph15050533 - 25 Apr 2022

Cited by 6 | Viewed by 2516

Abstract

Nivolumab (anti-PD-1 antibody) and atezolizumab (anti-PD-L1 antibody) have shown superior survival outcomes and improved adverse effects compared to standard chemotherapy in advanced non-small cell lung cancer (NSCLC) patients. However, the efficacy of both treatments has not been directly compared in clinical trials. This [...] Read more.

Nivolumab (anti-PD-1 antibody) and atezolizumab (anti-PD-L1 antibody) have shown superior survival outcomes and improved adverse effects compared to standard chemotherapy in advanced non-small cell lung cancer (NSCLC) patients. However, the efficacy of both treatments has not been directly compared in clinical trials. This retrospective, single-centre study was performed from June 2015 to December 2020 and included a cohort of 158 previously treated patients with stage IV or recurrent NSCLC who received PD-1 (nivolumab) (n = 89) or PD-L1 (atezolizumab) (n = 69) inhibitors at the Virgen del Rocío Hospital in Seville. The objective response rate (ORR) was 22.5% in the nivolumab group and 14.5% in the atezolizumab group (p = 0.140). Multivariate analysis did not show significant differences between the two groups for PFS and OS (PFS hazard ratio (HR): 0.80, 95% confidence interval (CI): 0.55–1.17, p = 0.260; OS HR: 0.79, 95% CI: 0.52–1.21, p = 0.281). Adverse events of all grades occurred in 68 patients in the nivolumab group (76.4%) and in 34 patients in the atezolizumab group (49.3%) (p < 0.001). Atezolizumab and nivolumab did not show statistically significant differences in survival outcomes in patients with NSCLC, even when stratified by histological subtype (squamous versus nonsquamous). However, the safety analysis suggested a more favourable toxicity profile for atezolizumab. Full article

(This article belongs to the Special Issue Advances in Non-small Cell Lung Cancer Treatment - Current and Future)

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9 pages, 1539 KiB

Open AccessArticle

Effectiveness and Cost-Effectiveness Profile of Second-Line Treatments with Nivolumab, Pembrolizumab and Atezolizumab in Patients with Advanced Non-Small Cell Lung Cancer

by Matteo Franchi, Giacomo Pellegrini and Giovanni Corrao

Pharmaceuticals 2022, 15(4), 489; https://doi.org/10.3390/ph15040489 - 18 Apr 2022

Cited by 6 | Viewed by 2454

Abstract

No evidence is available on the head-to-head comparison of clinical outcomes of patients treated with immune checkpoint inhibitors (ICIs) for advanced non-small cell lung cancer (NSCLC) in a real-world setting. We aimed to compare the effectiveness and cost-effectiveness profile of nivolumab, pembrolizumab and [...] Read more.

No evidence is available on the head-to-head comparison of clinical outcomes of patients treated with immune checkpoint inhibitors (ICIs) for advanced non-small cell lung cancer (NSCLC) in a real-world setting. We aimed to compare the effectiveness and cost-effectiveness profile of nivolumab, pembrolizumab and atezolizumab. We used a population-based retrospective cohort study based on the healthcare utilization databases of the Lombardy Region, Italy. The study cohort included all patients with a diagnosis of lung cancer, who started a second-line treatment for advanced NSCLC with nivolumab, pembrolizumab or atezolizumab from 2015 to 30 June 2020. Overall survival and average cumulative healthcare costs were measured from the start of second-line treatment until 31 December 2020. The study cohort included 1607 patients who started a second-line treatment with ICIs, of which there were 1193 with nivolumab, 138 with pembrolizumab and 276 with atezolizumab. No differences were observed between treatment arms in terms of sex, age or comorbidities. Median OS was very similar between groups, being 8.9, 9.4 and 8.7 months, respectively, in patients treated with nivolumab, pembrolizumab and atezolizumab (p = 0.898). The adjusted hazard ratio of death of patients treated with pembrolizumab and atezolizumab, as compared to nivolumab, were 1.01 (95% CI: 0.81 to 1.25) and 1.03 (0.88 to 1.21), respectively. Healthcare cumulative costs measured in the first two years of follow-up were EUR 43,764, 46,233 and 34,116, on average, associated with nivolumab, pembrolizumab and atezolizumab, respectively. In our real-world study, atezolizumab was the ICI associated with the most favorable cost-effectiveness profile. Full article

(This article belongs to the Special Issue Advances in Non-small Cell Lung Cancer Treatment - Current and Future)

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22 pages, 7251 KiB

Open AccessArticle

Studies on Preformulation and Formulation of JIN-001 Liquisolid Tablet with Enhanced Solubility

by Han-Sol Kim, Chang-Min Kim, An-Na Jo and Joo-Eun Kim

Pharmaceuticals 2022, 15(4), 412; https://doi.org/10.3390/ph15040412 - 28 Mar 2022

Cited by 4 | Viewed by 2982

Abstract

This study aimed to develop a heat shock protein 90 (Hsp90) inhibitor liquisolid tablet with improved solubility to overcome low bioavailability issues. As an active pharmaceutical ingredient (API), JIN-001, a novel Hsp90 inhibitor, was reported to have substantial in vitro antiproliferative and in [...] Read more.

This study aimed to develop a heat shock protein 90 (Hsp90) inhibitor liquisolid tablet with improved solubility to overcome low bioavailability issues. As an active pharmaceutical ingredient (API), JIN-001, a novel Hsp90 inhibitor, was reported to have substantial in vitro antiproliferative and in vivo antitumor activity; however, JIN-001 was a crystalline solid with very low solubility in an aqueous solution, and therefore, Capryol 90, which has excellent solubilization ability, was selected as an optimal liquid vehicle based on solubility studies. JIN-001 liquisolid (JLS) powder was successfully prepared by dissolving JIN-001 in Capryol 90 and mixing colloidal silicon dioxide (CSD) used as an oil adsorption agent. The prepared JLS was confirmed to be amorphous. Based on the result of the solubility test of JLS, compared to JIN-001, the solubility of the former was significantly improved in all solvents regardless of pH. JLS tablets were prepared through wet granulation using JIN-001 and stable excipients based on the compatibility test. The developed JLS tablet significantly increased the drug release rate in all tested solutions; however, the liquisolid method had no significant effect on bioavailability in the pharmacokinetics study in beagle dogs. In conclusion, the liquisolid system influenced the solubility and dissolution rate of JIN-001. Full article

(This article belongs to the Special Issue Advances in Non-small Cell Lung Cancer Treatment - Current and Future)

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19 pages, 3133 KiB

Open AccessArticle

Metformin Enhances TKI-Afatinib Cytotoxic Effect, Causing Downregulation of Glycolysis, Epithelial–Mesenchymal Transition, and EGFR-Signaling Pathway Activation in Lung Cancer Cells

by Pedro Barrios-Bernal, Norma Hernandez-Pedro, Mario Orozco-Morales, Rubí Viedma-Rodríguez, José Lucio-Lozada, Federico Avila-Moreno, Andrés F. Cardona, Rafael Rosell and Oscar Arrieta

Pharmaceuticals 2022, 15(3), 381; https://doi.org/10.3390/ph15030381 - 21 Mar 2022

Cited by 7 | Viewed by 3107

Abstract

The combination of metformin and TKIs for non-small cell lung cancer has been proposed as a strategy to overcome resistance of neoplastic cells induced by several molecular mechanisms. This study sought to investigate the effects of a second generation TKI afatinib, metformin, or [...] Read more.

The combination of metformin and TKIs for non-small cell lung cancer has been proposed as a strategy to overcome resistance of neoplastic cells induced by several molecular mechanisms. This study sought to investigate the effects of a second generation TKI afatinib, metformin, or their combination on three adenocarcinoma lung cancer cell lines with different EGFRmutation status. A549, H1975, and HCC827 cell lines were treated with afatinib, metformin, and their combination for 72 h. Afterwards, several parameters were assessed including cytotoxicity, interactions, apoptosis, and EGFR protein levels at the cell membrane and several glycolytic, oxidative phosphorylation (OXPHOS), and EMT expression markers. All cell lines showed additive to synergic interactions for the induction of cytotoxicity caused by the tested combination, as well as an improved pro-apoptotic effect. This effect was accompanied by downregulation of glycolytic, EMT markers, a significant decrease in glucose uptake, extracellular lactate, and a tendency towards increased OXPHOS subunits expression. Interestingly, we observed a better response to the combined therapy in lung cancer cell lines A549 and H1975, which normally have low affinity for TKI treatment. Findings from this study suggest a sensitization to afatinib therapy by metformin in TKI-resistant lung cancer cells, as well as a reduction in cellular glycolytic phenotype. Full article

(This article belongs to the Special Issue Advances in Non-small Cell Lung Cancer Treatment - Current and Future)

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Review

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30 pages, 2210 KiB

Open AccessReview

Targeting Inflammation in Non-Small Cell Lung Cancer through Drug Repurposing

by Thiviyadarshini Rajasegaran, Chee Wun How, Anoosha Saud, Azhar Ali and Jonathan Chee Woei Lim

Pharmaceuticals 2023, 16(3), 451; https://doi.org/10.3390/ph16030451 - 16 Mar 2023

Cited by 10 | Viewed by 5139

Abstract

Lung cancer is the most common cause of cancer-related deaths. Lung cancers can be classified 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 [...] Read more.

Lung cancer is the most common cause of cancer-related deaths. Lung cancers can be classified 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. Full article

(This article belongs to the Special Issue Advances in Non-small Cell Lung Cancer Treatment - Current and Future)

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22 pages, 1448 KiB

Open AccessReview

Targeting the DNA Damage Response Machinery for Lung Cancer Treatment

by Katharigatta N. Venugopala

Pharmaceuticals 2022, 15(12), 1475; https://doi.org/10.3390/ph15121475 - 27 Nov 2022

Cited by 7 | Viewed by 2216

Abstract

Lung cancer is considered the most commonly diagnosed cancer and one of the leading causes of death globally. Despite the responses from small-cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) patients to conventional chemo- and radiotherapies, the current outcomes are not [...] Read more.

Lung cancer is considered the most commonly diagnosed cancer and one of the leading causes of death globally. Despite the responses from small-cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) patients to conventional chemo- and radiotherapies, the current outcomes are not satisfactory. Recently, novel advances in DNA sequencing technologies have started to take off which have provided promising tools for studying different tumors for systematic mutation discovery. To date, a limited number of DDR inhibition trials have been conducted for the treatment of SCLC and NSCLC patients. However, strategies to test different DDR inhibitor combinations or to target multiple pathways are yet to be explored. With the various biomarkers that have either been recently discovered or are the subject of ongoing investigations, it is hoped that future trials would be designed to allow for studying targeted treatments in a biomarker-enriched population, which is defensible for the improvement of prognosis for SCLC and NSCLC patients. This review article sheds light on the different DNA repair pathways and some of the inhibitors targeting the proteins involved in the DNA damage response (DDR) machinery, such as ataxia telangiectasia and Rad3-related protein (ATR), DNA-dependent protein kinase (DNA-PK), and poly-ADP-ribose polymerase (PARP). In addition, the current status of DDR inhibitors in clinical settings and future perspectives are discussed. Full article

(This article belongs to the Special Issue Advances in Non-small Cell Lung Cancer Treatment - Current and Future)

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22 pages, 1059 KiB

Open AccessReview

Will We Unlock the Benefit of Metformin for Patients with Lung Cancer? Lessons from Current Evidence and New Hypotheses

by Pedro Barrios-Bernal, Zyanya Lucia Zatarain-Barrón, Norma Hernández-Pedro, Mario Orozco-Morales, Alejandra Olivera-Ramírez, Federico Ávila-Moreno, Ana Laura Colín-González, Andrés F. Cardona, Rafael Rosell and Oscar Arrieta

Pharmaceuticals 2022, 15(7), 786; https://doi.org/10.3390/ph15070786 - 24 Jun 2022

Cited by 9 | Viewed by 2566

Abstract

Metformin has been under basic and clinical study as an oncological repurposing pharmacological agent for several years, stemming from observational studies which consistently evidenced that subjects who were treated with metformin had a reduced risk for development of cancer throughout their lives, as [...] Read more.

Metformin has been under basic and clinical study as an oncological repurposing pharmacological agent for several years, stemming from observational studies which consistently evidenced that subjects who were treated with metformin had a reduced risk for development of cancer throughout their lives, as well as improved survival outcomes when diagnosed with neoplastic diseases. As a result, several basic science studies have attempted to dissect the relationship between metformin’s metabolic mechanism of action and antineoplastic cellular signaling pathways. Evidence in this regard was compelling enough that a myriad of randomized clinical trials was planned and conducted in order to establish the effect of metformin treatment for patients with diverse neoplasms, including lung cancer. As with most novel antineoplastic agents, early results from these studies have been mostly discouraging, though a recent analysis that incorporated body mass index may provide significant information regarding which patient subgroups might derive the most benefit from the addition of metformin to their anticancer treatment. Much in line with the current pipeline for anticancer agents, it appears that the benefit of metformin may be circumscribed to a specific patient subgroup. If so, addition of metformin to antineoplastic agents could prove one of the most cost-effective interventions proposed in the context of precision oncology. Currently published reviews mostly rely on a widely questioned mechanism of action by metformin, which fails to consider the differential effects of the drug in lean vs. obese subjects. In this review, we analyze the pre-clinical and clinical information available to date regarding the use of metformin in various subtypes of lung cancer and, further, we present evidence as to the differential metabolic effects of metformin in lean and obese subjects where, paradoxically, the obese subjects have reported more benefit with the addition of metformin treatment. The novel mechanisms of action described for this biguanide may explain the different results observed in clinical trials published in the last decade. Lastly, we present novel hypothesis regarding potential biomarkers to identify who might reap benefit from this intervention, including the role of prolyl hydroxylase domain 3 (PHD3) expression to modify metabolic phenotypes in malignant diseases. Full article

(This article belongs to the Special Issue Advances in Non-small Cell Lung Cancer Treatment - Current and Future)

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53 pages, 2656 KiB

Open AccessEditor’s ChoiceReview

Targeting Nuclear Receptors in Lung Cancer—Novel Therapeutic Prospects

by Shailendra Kumar Gangwar, Aviral Kumar, Kenneth Chun-Hong Yap, Sandra Jose, Dey Parama, Gautam Sethi, Alan Prem Kumar and Ajaikumar B. Kunnumakkara

Pharmaceuticals 2022, 15(5), 624; https://doi.org/10.3390/ph15050624 - 18 May 2022

Cited by 10 | Viewed by 4583

Abstract

Lung cancer, the second most commonly diagnosed cancer, is the major cause of fatalities worldwide for both men and women, with an estimated 2.2 million new incidences and 1.8 million deaths, according to GLOBOCAN 2020. Although various risk factors for lung cancer pathogenesis [...] Read more.

Lung cancer, the second most commonly diagnosed cancer, is the major cause of fatalities worldwide for both men and women, with an estimated 2.2 million new incidences and 1.8 million deaths, according to GLOBOCAN 2020. Although various risk factors for lung cancer pathogenesis have been reported, controlling smoking alone has a significant value as a preventive measure. In spite of decades of extensive research, mechanistic cues and targets need to be profoundly explored to develop potential diagnostics, treatments, and reliable therapies for this disease. Nuclear receptors (NRs) function as transcription factors that control diverse biological processes such as cell growth, differentiation, development, and metabolism. The aberrant expression of NRs has been involved in a variety of disorders, including cancer. Deregulation of distinct NRs in lung cancer has been associated with numerous events, including mutations, epigenetic modifications, and different signaling cascades. Substantial efforts have been made to develop several small molecules as agonists or antagonists directed to target specific NRs for inhibiting tumor cell growth, migration, and invasion and inducing apoptosis in lung cancer, which makes NRs promising candidates for reliable lung cancer therapeutics. The current work focuses on the importance of various NRs in the development and progression of lung cancer and highlights the different small molecules (e.g., agonist or antagonist) that influence NR expression, with the goal of establishing them as viable therapeutics to combat lung cancer. Full article

(This article belongs to the Special Issue Advances in Non-small Cell Lung Cancer Treatment - Current and Future)

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