Evolving Strategies in NSCLC Care: Targeted Therapies,
Biomarkers, Predictive Models, and Patient Management

Janmejay      Pant; Payal      Mittal; Lovedeep      Singh; Harneet      Marwah
doi:10.2174/0118756921301200240427053840
Abstract

Lung cancer, primarily Non-Small Cell Lung Cancer (NSCLC), is a global public health concern responsible for 80-85% of cases, with over two million new cases occurring annually, and 50% of them in Asia. While there has been a gradual reduction in United States (US) cases over the last decade, with 238,340 new cases and 127,070 deaths reported in 2023, managing metastatic NSCLC remains crucial, focusing on prolonging survival and enhancing quality of life. Integration of early palliative care shows promise in this regard. International guidelines recommend personalized treatment guided by genetic mutations (Epidermal Growth Factor Receptor (EGFR), Anaplastic Lymphoma Kinase, C-Ros oncogene [1ROS1]) and systemic therapies, including chemotherapy, targeted therapy, and immunotherapy, which play pivotal roles in redefining care. Treatment effectiveness hinges on factors such as cancer stage, patient health, and therapy type, with surgery and radiation therapy common in early stages and advanced stages requiring chemotherapy, targeted therapy, or immunotherapy. Despite advancements in treatment modalities, NSCLC continues to pose a significant challenge globally, particularly in Asia, where a substantial portion of new cases arise. While there has been an uncertain reduction in the incidence of lung cancer in the US over the past decade, the burden of the disease persists, with substantial mortality rates reported annually.
Additionally, upon diagnosis, many NSCLC patients present with distant metastases, necessitating effective treatment strategies to improve overall survival and quality of life. The objectives include investigating targeted treatments for NSCLC with specific genetic mutations, examining mechanisms of novel therapies under study, evaluating preclinical and clinical studies for therapy efficacy and safety, identifying genetic and epigenetic biomarkers for diagnosis, prognosis, and treatment selection, developing predictive models for lung cancer recurrence and survival, assessing the efficacy of treatment approaches for early-stage lung cancer, and enhancing patient outcomes through collaborative care and lifestyle interventions. These collective efforts promise to improve patient outcomes and quality of life in the battle against NSCLC.
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[1]
Azar I, Alkassis S, Fukui J, et al. Spotlight on trastuzumab deruxtecan (DS-8201,T-DXd) for HER2 mutation positive non-small cell lung cancer. Lung Cancer  2021; 12: 103-14.
 [http://dx.doi.org/10.2147/LCTT.S307324] [PMID: 34675733]

[2]
Cao W, Chen HD, Yu YW, Li N, Chen WQ. Changing profiles of cancer burden worldwide and in China: A secondary analysis of the global cancer statistics 2020. Chin Med J  2021; 134(7): 783-91.
 [http://dx.doi.org/10.1097/CM9.0000000000001474] [PMID: 33734139]

[3]
Chen P, Liu Y, Wen Y, Zhou C. Non‐small cell lung cancer in China. Cancer Commun  2022; 42(10): 937-70.
 [http://dx.doi.org/10.1002/cac2.12359] [PMID: 36075878]

[4]
Gao S, Li N, Wang S, et al. Lung Cancer in People’s Republic of China. J Thorac Oncol  2020; 15(10): 1567-76.
 [http://dx.doi.org/10.1016/j.jtho.2020.04.028] [PMID: 32981600]

[5]
Luo YH, Chiu CH, Kuo SCH, et al. Lung cancer in republic of china. J Thorac Oncol  2021; 16(4): 519-27.
 [http://dx.doi.org/10.1016/j.jtho.2020.10.155] [PMID: 33781442]

[6]
Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics. CA Cancer J Clin  2022; 72(1): 7-33.
 [http://dx.doi.org/10.3322/caac.21708] [PMID: 35020204]

[7]
Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin  2021; 71(3): 209-49.
 [http://dx.doi.org/10.3322/caac.21660] [PMID: 33538338]

[8]
Zhang S, Sun K, Zheng R, et al. Cancer incidence and mortal-ity in China, 2015. J National Cancer Center  2021; 1(1): 2-11.
 [http://dx.doi.org/10.1016/j.jncc.2020.12.001]

[9]
 American Cancer Society. Key Statistics for Lung Cancer. 2023. Available from: https://www.cancer.org/ [Last Revised: January 12].

[10]
Wang L. Deep learning techniques to diagnose lung cancer. cancers  2022; 14(22): 5569.
 [http://dx.doi.org/10.3390/cancers14225569] [PMID: 36428662]

[11]
Marwah H, Pant J, Yadav J, Shah K, Dewangan HK. Biosen-sor detection of COVID-19 in lung cancer: Hedgehog and Mucin Signaling Insights. Curr Pharm Des  2023; 29(43): 3442-57.
 [http://dx.doi.org/10.2174/0113816128276948231204111531] [PMID: 38270161]

[12]
Temel JS, Greer JA, Muzikansky A, et al. Early palliative care for patients with metastatic non-small-cell lung cancer. N Engl J Med  2010; 363(8): 733-42.
 [http://dx.doi.org/10.1056/NEJMoa1000678] [PMID: 20818875]

[13]
Forde PM, Ettinger DS. Targeted therapy for non-small-cell lung cancer: Past, present and future. Expert Rev Anticancer Ther  2013; 13(6): 745-58.
 [http://dx.doi.org/10.1586/era.13.47] [PMID: 23773106]

[14]
Ettinger DS, Wood DE, Aisner DL, et al. NCCN Guidelines Insights: non–small cell lung cancer, Version 2. J Natl Compr Canc Netw  2021; 19(3): 254-66.
 [http://dx.doi.org/10.6004/jnccn.2021.0013] [PMID: 33668021]

[15]
Lindeman NI, Cagle PT, Beasley MB, et al. Molecular testing guideline for selection of lung cancer patients for EGFR and ALK tyrosine kinase inhibitors: Guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology. J Mol Diagn  2013; 15(4): 415-53.
 [http://dx.doi.org/10.1016/j.jmoldx.2013.03.001] [PMID: 23562183]

[16]
Pieniążek M, Pawlak P, Radecka B. Early palliative care of non-small cell lung cancer in the context of immunotherapy. Oncol Lett  2020; 20(6): 396.
 [PMID: 33193856]

[17]
Fu M, Travier N, Sánchez MJC, Sánchez MJM, Vidal C, Gar-cia M. Identifying high-risk individuals for lung cancer screening: Going beyond NLST criteria. PLoS One  2018; 13(4): e0195441.
 [http://dx.doi.org/10.1371/journal.pone.0195441] [PMID: 29621354]

[18]
Bonney A, Malouf R, Marchal C, et al. Impact of low-dose computed tomography (LDCT) screening on lung cancer-related mortality. Cochrane Database Syst Rev  2022; 8(8): CD013829.
 [PMID: 35921047]

[19]
Amicizia D, Piazza MF, Marchini F, et al. Systematic review of lung cancer screening: Advancements and strategies for implementation. Health Care  2023; 11(14): 2085.
 [http://dx.doi.org/10.3390/healthcare11142085] [PMID: 37510525]

[20]
Li C, Wang H, Jiang Y, et al. Advances in lung cancer screening and early detection. Cancer Biol Med  2022; 19(5): 591-608.
 [http://dx.doi.org/10.20892/j.issn.2095-3941.2021.0690] [PMID: 35535966]

[21]
Jonas DE, Reuland DS, Reddy SM, et al. Screening for lung cancer with low-dose computed tomography. JAMA  2021; 325(10): 971-87.
 [http://dx.doi.org/10.1001/jama.2021.0377] [PMID: 33687468]

[22]
Ramaswamy A. Lung cancer screening: Review and 2021 update. Curr Pulmonol Rep  2022; 11(1): 15-28.
 [http://dx.doi.org/10.1007/s13665-021-00283-1] [PMID: 35402145]

[23]
Molina JR, Yang P, Cassivi SD, Schild SE, Adjei AA. Non-small cell lung cancer: Epidemiology, risk factors, treatment, and survivorship. Mayo Clin Proc  2008; 83(5): 584-94.
 [http://dx.doi.org/10.1016/S0025-6196(11)60735-0] [PMID: 18452692]

[24]
Nishino M, Jackman DM, Hatabu H, Jänne PA, Johnson BE, Van den Abbeele AD. Imaging of lung cancer in the era of molecular medicine. Acad Radiol  2011; 18(4): 424-36.
 [http://dx.doi.org/10.1016/j.acra.2010.10.020] [PMID: 21277232]

[25]
Testa U, Castelli G, Pelosi E. Lung cancers: Molecular characterization, clonal heterogeneity and evolution, and cancer stem cells. Cancers  2018; 10(8): 248.
 [http://dx.doi.org/10.3390/cancers10080248] [PMID: 30060526]

[26]
Desai A, Menon SP, Dy GK. Alterations in genes other than EGFR/ALK/ROS1 in non-small cell lung cancer: Trials and treatment options. Cancer Biol Med  2016; 13(1): 77-86.
 [http://dx.doi.org/10.20892/j.issn.2095-3941.2016.0008] [PMID: 27144064]

[27]
Aragon KN. Palliative care in lung cancer. Clin Chest Med  2020; 41(2): 281-93.
 [http://dx.doi.org/10.1016/j.ccm.2020.02.005] [PMID: 32402363]

[28]
Karachaliou N, Bruno KM, Bracht JWP, Rosell R. EGFR first- and second-generation TKIs—there is still place for them in EGFR-mutant NSCLC patients. Transl Cancer Res  2018; 8(S1): S23-47.
 [http://dx.doi.org/10.21037/tcr.2018.10.06] [PMID: 35117062]

[29]
Cameron LB, Hitchen N, Chandran E, et al. Targeted therapy for advanced anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer. Cochrane Database Syst Rev  2022; 1(1): CD013453.
 [PMID: 34994987]

[30]
Zubair T, Bandyopadhyay D. Small molecule EGFR inhibitors as anti-cancer agents: Discovery, mechanisms of action, and opportunities. Int J Mol Sci  2023; 24(3): 2651.
 [http://dx.doi.org/10.3390/ijms24032651] [PMID: 36768973]

[31]
Xu C, Lei L, Wang W, et al. Molecular characteristics and clinical outcomes of EGFR exon 19 C-Helix deletion in non–small cell lung cancer and response to EGFR TKIs. Transl Oncol  2020; 13(9): 100791.
 [http://dx.doi.org/10.1016/j.tranon.2020.100791] [PMID: 32492620]

[32]
Golding B, Luu A, Jones R, Petit VAM. The function and therapeutic targeting of anaplastic lymphoma kinase (ALK) in non-small cell lung cancer (NSCLC). Mol Cancer  2018; 17(1): 52.
 [http://dx.doi.org/10.1186/s12943-018-0810-4] [PMID: 29455675]

[33]
D’Angelo A, Sobhani N, Chapman R, et al. Focus on ROS1-positive non-small cell lung cancer (NSCLC): Crizotinib, resistance mechanisms and the newer generation of targeted therapies. Cancers  2020; 12(11): 3293.
 [http://dx.doi.org/10.3390/cancers12113293] [PMID: 33172113]

[34]
Gendarme S, Bylicki O, Chouaid C, Guisier F. ROS-1 fusions in non-small-cell lung cancer: Evidence to date. Curr Oncol  2022; 29(2): 641-58.
 [http://dx.doi.org/10.3390/curroncol29020057] [PMID: 35200557]

[35]
Hussain MRM, Baig M, Mohamoud HSA, et al. BRAF gene: From human cancers to developmental syndromes. Saudi J Biol Sci  2015; 22(4): 359-73.
 [http://dx.doi.org/10.1016/j.sjbs.2014.10.002] [PMID: 26150740]

[36]
Yan N, Guo S, Zhang H, Zhang Z, Shen S, Li X. BRAF-mutated non-small cell lung cancer: Current treatment status and future perspective. Front Oncol  2022; 12: 863043.
 [http://dx.doi.org/10.3389/fonc.2022.863043] [PMID: 35433454]

[37]
Proietti I, Skroza N, Michelini S, et al. BRAF inhibitors: molecular targeting and immunomodulatory actions. Cancers  2020; 12(7): 1823.
 [http://dx.doi.org/10.3390/cancers12071823] [PMID: 32645969]

[38]
Chen D, Zhang LQ, Huang JF, et al. BRAF mutations in patients with non-small cell lung cancer: A systematic review and meta-analysis. PLoS One  2014; 9(6): e101354.
 [http://dx.doi.org/10.1371/journal.pone.0101354] [PMID: 24979348]

[39]
Collie GW, Barlind L, Bazzaz S, et al. Discovery of a selective c-MET inhibitor with a novel binding mode. Bioorg Med Chem Lett  2022; 75: 128948.
 [http://dx.doi.org/10.1016/j.bmcl.2022.128948] [PMID: 35987508]

[40]
Drusbosky LM, Dawar R, Rodriguez E, Ikpeazu CV. Thera-peutic strategies in METex14 skipping mutated non-small cell lung cancer. J Hematol Oncol  2021; 14(1): 129.
 [http://dx.doi.org/10.1186/s13045-021-01138-7] [PMID: 34425853]

[41]
Reck M, Carbone DP, Garassino M, Barlesi F. Targeting KRAS in non-small-cell lung cancer: Recent progress and new approaches. Ann Oncol  2021; 32(9): 1101-10.
 [http://dx.doi.org/10.1016/j.annonc.2021.06.001] [PMID: 34089836]

[42]
Nakajima EC, Drezner N, Li X, et al. FDA Approval Summary: Sotorasib for KRAS G12C -Mutated Metastatic NSCLC. Clin Cancer Res  2022; 28(8): 1482-6.
 [http://dx.doi.org/10.1158/1078-0432.CCR-21-3074] [PMID: 34903582]

[43]
Canon J, Rex K, Saiki AY, et al. The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity. Nature  2019; 575(7781): 217-23.
 [http://dx.doi.org/10.1038/s41586-019-1694-1] [PMID: 31666701]

[44]
Rekhtman N, Ang DC, Riely GJ, Ladanyi M, Moreira AL. KRAS mutations are associated with solid growth pattern and tumor-infiltrating leukocytes in lung adenocarcinoma. Mod Pathol  2013; 26(10): 1307-19.
 [http://dx.doi.org/10.1038/modpathol.2013.74] [PMID: 23619604]

[45]
Drilon A, Hu ZI, Lai GGY, Tan DSW. Targeting RET-driven cancers: Lessons from evolving preclinical and clinical land-scapes. Nat Rev Clin Oncol  2018; 15(3): 151-67.
 [http://dx.doi.org/10.1038/nrclinonc.2017.175] [PMID: 29134959]

[46]
Bronte G, Ulivi P, Verlicchi A, Cravero P, Delmonte A, Crinò L. Targeting RET-rearranged non-small-cell lung cancer: Future prospects. Lung Cancer  2019; 10: 27-36.
 [http://dx.doi.org/10.2147/LCTT.S192830] [PMID: 30962732]

[47]
Ferrara R, Auger N, Auclin E, Besse B. Clinical and translational implications of RET rearrangements in non–small cell lung Cancer. J Thorac Oncol  2018; 13(1): 27-45.
 [http://dx.doi.org/10.1016/j.jtho.2017.10.021] [PMID: 29128428]

[48]
Wright KM. FDA approves pralsetinib for treatment of adults with metastatic RET fusion-positive NSCLC. Oncology  2020; 34(10): 406-31.

[49]
Nguyen L, Monestime S. Pralsetinib: Treatment of metastatic RET fusion–positive non–small cell lung cancer. Am J Health Syst Pharm  2022; 79(7): 527-33.
 [http://dx.doi.org/10.1093/ajhp/zxab462] [PMID: 34864862]

[50]
Melincovici CS, Boşca AB, Şuşman S, et al. Vascular endo-thelial growth factor (VEGF) - key factor in normal and pathological angiogenesis. Rom J Morphol Embryol  2018; 59(2): 455-67.
 [PMID: 30173249]

[51]
Cazares AD, Dominguez CR, Reyes CA, Camarillo LC. Hernadez de la Cruz ON, Gonzalez LJS. Contribution of angio-genesis to inflammation and cancer. Front Oncol  2019; 9: 1399.
 [http://dx.doi.org/10.3389/fonc.2019.01399] [PMID: 31921656]

[52]
Le X, Nilsson M, Goldman J, et al. Dual EGFR-VEGF path-way inhibition: A promising strategy for patients with EGFR-mutant NSCLC. J Thorac Oncol  2021; 16(2): 205-15.
 [http://dx.doi.org/10.1016/j.jtho.2020.10.006] [PMID: 33096270]

[53]
Hafner S. First-line anti-VEGF plus EGFR-TKI in EGFR-mutant NSCLC: Adding the ARTEMIS trial to the puzzle of current evidence. Signal Transduct Target Ther  2021; 6(1): 417.
 [http://dx.doi.org/10.1038/s41392-021-00813-y] [PMID: 34873145]

[54]
Westover D, Zugazagoitia J, Cho BC, Lovly CM, Paz-Ares L. Mechanisms of acquired resistance to first- and second-generation EGFR tyrosine kinase inhibitors. Ann Oncol  2018; 29(S1): i10-9.
 [http://dx.doi.org/10.1093/annonc/mdx703] [PMID: 29462254]

[55]
Maemondo M, Inoue A, Kobayashi K, et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med  2010; 362(25): 2380-8.
 [http://dx.doi.org/10.1056/NEJMoa0909530] [PMID: 20573926]

[56]
Liang JL, Ren XC, Lin Q. Treating advanced non-small-cell lung cancer in Chinese patients: Focus on icotinib. OncoTargets Ther  2014; 7: 761-70.
 [PMID: 24876785]

[57]
Juan O, Popat S. Treatment choice in epidermal growth factor receptor mutation-positive non-small cell lung carcinoma: Latest evidence and clinical implications. Ther Adv Med Oncol  2017; 9(3): 201-16.
 [http://dx.doi.org/10.1177/1758834016687262] [PMID: 28344665]

[58]
Lavacchi D, Mazzoni F, Giaccone G. Clinical evaluation of dacomitinib for the treatment of metastatic non-small cell lung cancer (NSCLC): Current perspectives. Drug Des Devel Ther  2019; 13: 3187-98.
 [http://dx.doi.org/10.2147/DDDT.S194231] [PMID: 31564835]

[59]
Le T, Gerber D. Newer-Generation EGFR Inhibitors in Lung Cancer: How Are They Best Used? Cancers  2019; 11(3): 366.
 [http://dx.doi.org/10.3390/cancers11030366] [PMID: 30875928]

[60]
Prabhash K, Noronha V, Joshi A, Desai S, Sahu A. Crizo-tinib: A comprehensive review. South Asian J Cancer  2013; 2(2): 91-7.
 [http://dx.doi.org/10.4103/2278-330X.110506] [PMID: 24455567]

[61]
Xia B, Nagasaka M, Zhu VW, Ou SHI, Soo RA. How to select the best upfront therapy for metastatic disease? Focus on ALK-rearranged non-small cell lung cancer (NSCLC). Transl Lung Cancer Res  2020; 9(6): 2521-34.
 [http://dx.doi.org/10.21037/tlcr-20-331] [PMID: 33489815]

[62]
Wang Y, Yuan X, Xiong J, et al. Pharmacology and clinical evaluation of ensartinib hydrochloride capsule. Zhongguo Fei Ai Za Zhi  2020; 23(8): 719-29.
 [PMID: 32838492]

[63]
Horn L, Wang Z, Wu G, et al. Ensartinib vs Crizotinib for Patients With Anaplastic Lymphoma Kinase−Positive Non–Small Cell Lung Cancer. JAMA Oncol  2021; 7(11): 1617-25.
 [http://dx.doi.org/10.1001/jamaoncol.2021.3523] [PMID: 34473194]

[64]
Shaw AT, Riely GJ, Bang YJ, et al. Crizotinib in ROS1-rearranged advanced non-small-cell lung cancer (NSCLC): Updated results, including overall survival, from PROFILE 1001. Ann Oncol  2019; 30(7): 1121-6.
 [http://dx.doi.org/10.1093/annonc/mdz131] [PMID: 30980071]

[65]
Azelby CM, Sakamoto MR, Bowles DW. ROS1 Targeted Therapies: Current Status. Curr Oncol Rep  2021; 23(8): 94.
 [http://dx.doi.org/10.1007/s11912-021-01078-y] [PMID: 34125313]

[66]
Drilon A, Siena S, Dziadziuszko R, et al. Entrectinib in ROS1 fusion-positive non-small-cell lung cancer: Integrated analysis of three phase 1–2 trials. Lancet Oncol  2020; 21(2): 261-70.
 [http://dx.doi.org/10.1016/S1470-2045(19)30690-4] [PMID: 31838015]

[67]
Dziadziuszko R, Krebs MG, De Braud F, et al. Updated integrated analysis of the efficacy and safety of entrectinib in locally advanced or metastatic ROS1 fusion–positive non–small-cell lung cancer. J Clin Oncol  2021; 39(11): 1253-63.
 [http://dx.doi.org/10.1200/JCO.20.03025] [PMID: 33646820]

[68]
Auliac JB, Bayle S, Do P, et al. Efficacy of dabrafenib plus trametinib combination in patients with BRAF V600E-mutant NSCLC in real-world setting: GFPC 01-2019. Cancers  2020; 12(12): 3608.
 [http://dx.doi.org/10.3390/cancers12123608] [PMID: 33276639]

[69]
Paik PK, Felip E, Veillon R, et al. Tepotinib in non–small-cell lung cancer with MET exon 14 skipping mutations. N Engl J Med  2020; 383(10): 931-43.
 [http://dx.doi.org/10.1056/NEJMoa2004407] [PMID: 32469185]

[70]
Wu YL, Smit EF, Bauer TM. Capmatinib for patients with non-small cell lung cancer with MET exon 14 skipping mutations: A review of preclinical and clinical studies. Cancer Treat Rev  2021; 95: 102173.
 [http://dx.doi.org/10.1016/j.ctrv.2021.102173] [PMID: 33740553]

[71]
Hong DS, Fakih MG, Strickler JH, et al. KRAS G12C inhibition with sotorasib in advanced solid tumors. N Engl J Med  2020; 383(13): 1207-17.
 [http://dx.doi.org/10.1056/NEJMoa1917239] [PMID: 32955176]

[72]
Drilon A, Oxnard GR, Tan DSW, et al. Efficacy of selpercatinib in RET fusion–positive non–small-cell lung cancer. N Engl J Med  2020; 383(9): 813-24.
 [http://dx.doi.org/10.1056/NEJMoa2005653] [PMID: 32846060]

[73]
Cascetta P, Sforza V, Manzo A, et al. RET inhibitors in non-small-cell lung cancer. Cancers  2021; 13(17): 4415.
 [http://dx.doi.org/10.3390/cancers13174415] [PMID: 34503226]

[74]
Qin H, Patel M. The challenge and opportunity of NTRK inhibitors in non-small cell lung cancer. Int J Mol Sci  2022; 23(6): 2916.
 [http://dx.doi.org/10.3390/ijms23062916] [PMID: 35328336]

[75]
Riudavets M, Sullivan I, Abdayem P, Planchard D. Targeting HER2 in non-small-cell lung cancer (NSCLC): A glimpse of hope? An updated review on therapeutic strategies in NSCLC harbouring HER2 alterations. ESMO Open  2021; 6(5): 100260.
 [http://dx.doi.org/10.1016/j.esmoop.2021.100260] [PMID: 34479034]

[76]
Li BT, Shen R, Buonocore D, et al. Ado-trastuzumab emtansine for patients with HER2 -mutant lung cancers: Results from a phase II basket trial. J Clin Oncol  2018; 36(24): 2532-7.
 [http://dx.doi.org/10.1200/JCO.2018.77.9777] [PMID: 29989854]

[77]
Bahadar H, Maqbool F, Niaz K, Abdollahi M. Toxicity of nanoparticles and an overview of current experimental models. Iran Biomed J  2016; 20(1): 1-11.
 [PMID: 26286636]

[78]
Im K, Mareninov S, Diaz MFP, Yong WH. An introduction to performing immunofluorescence staining. Methods Mol Biol  2019; 1897: 299-311.
 [http://dx.doi.org/10.1007/978-1-4939-8935-5_26] [PMID: 30539454]

[79]
Mirzayans R, Murray D. Do TUNEL and other apoptosis assays detect cell death in preclinical studies? Int J Mol Sci  2020; 21(23): 9090.
 [http://dx.doi.org/10.3390/ijms21239090] [PMID: 33260475]

[80]
Kastoori PL, Geschwender SAR, Harford JA. A systematic approach to quantitative Western blot analysis. Anal Biochem  2020; 593: 113608.
 [http://dx.doi.org/10.1016/j.ab.2020.113608] [PMID: 32007473]

[81]
Stoddart MJ. Cell viability assays: Introduction. Methods Mol Biol  2011; 740: 1-6.
 [http://dx.doi.org/10.1007/978-1-61779-108-6_1] [PMID: 21468961]

[82]
Lallo A, Schenk MW, Frese KK, Blackhall F, Dive C. Circulating tumor cells and CDX models as a tool for preclinical drug development. Transl Lung Cancer Res  2017; 6(4): 397-408.
 [http://dx.doi.org/10.21037/tlcr.2017.08.01] [PMID: 28904884]

[83]
Yoshida GJ. Applications of patient-derived tumor xenograft models and tumor organoids. J Hematol Oncol  2020; 13(1): 4.
 [http://dx.doi.org/10.1186/s13045-019-0829-z] [PMID: 31910904]

[84]
Sheridan C, Downward J. Overview of KRAS-driven genetically engineered mouse models of non-small cell lung cancer. Curr Protoc Pharmacol  2015; 70: 14.35.1-14.35.16.

[85]
Thawani R, McLane M, Beig N, et al. Radiomics and radiogenomics in lung cancer: A review for the clinician. Lung Cancer  2018; 115: 34-41.
 [http://dx.doi.org/10.1016/j.lungcan.2017.10.015] [PMID: 29290259]

[86]
van Meerbeeck JP, Fennell DA, De Ruysscher DKM. Small-cell lung cancer. Lancet  2011; 378(9804): 1741-55.
 [http://dx.doi.org/10.1016/S0140-6736(11)60165-7] [PMID: 21565397]

[87]
Remon J, Steuer CE, Ramalingam SS, Felip E. Osimertinib and other third-generation EGFR TKI in EGFR-mutant NSCLC patients. Ann Oncol  2018; 29(S1): i20-7.
 [http://dx.doi.org/10.1093/annonc/mdx704] [PMID: 29462255]

[88]
Smit EF, de Langen AJ. Pembrolizumab for all PD-L1-positive NSCLC. Lancet  2019; 393(10183): 1776-8.
 [http://dx.doi.org/10.1016/S0140-6736(18)32559-5] [PMID: 30955976]

[89]
Shaw AT, Bauer TM, de Marinis F, et al. First-line lorlatinib or crizotinib in advanced ALK -positive lung cancer. N Engl J Med  2020; 383(21): 2018-29.
 [http://dx.doi.org/10.1056/NEJMoa2027187] [PMID: 33207094]

[90]
Camidge DR, Kim HR, Ahn MJ, et al. Brigatinib versus crizotinib in ALK inhibitornaive advanced ALK-positive NSCLC: Final results of phase 3 ALTA-1L trial. J Thorac Oncol  2021; 16(12): 2091-108.
 [http://dx.doi.org/10.1016/j.jtho.2021.07.035] [PMID: 34537440]

[91]
McCoach CE, Yu A, Gandara DR, et al. Phase I/II study of capmatinib plus erlotinib in patients with MET-positive non–small-cell lung cancer. JCO Precis Oncol  2021; 1(5): 177-90.
 [http://dx.doi.org/10.1200/PO.20.00279] [PMID: 34036220]

[92]
Araujo JM, Gomez AC, Pinto JA, Rolfo C, Raez LE. Profile of entrectinib in the treatment of ROS1-positive non-small cell lung cancer: Evidence to date. Hematol Oncol Stem Cell Ther  2021; 14(3): 192-8.
 [http://dx.doi.org/10.1016/j.hemonc.2020.11.005] [PMID: 33290717]

[93]
Herceg Z, Hainaut P. Genetic and epigenetic alterations as biomarkers for cancer detection, diagnosis and prognosis. Mol Oncol  2007; 1(1): 26-41.
 [http://dx.doi.org/10.1016/j.molonc.2007.01.004] [PMID: 19383285]

[94]
Zhao J, Han Y, Li J, Chai R, Bai C. Prognostic value of KRAS/TP53/PIK3CA in non small cell lung cancer. Oncol Lett  2019; 17(3): 3233-40.
 [http://dx.doi.org/10.3892/ol.2019.10012] [PMID: 30867754]

[95]
Sharma S, Kelly TK, Jones PA. Epigenetics in cancer. Carcinogenesis  2010; 31(1): 27-36.
 [http://dx.doi.org/10.1093/carcin/bgp220] [PMID: 19752007]

[96]
Lee JU, Sul HJ, Son JW. Promoter methylation of CDKN2A, RARβ and RASSF1A in non-small cell lung carcinoma: Quantitative evaluation using pyrosequencing. Tuberc Respir Dis  2012; 73(1): 11-21.
 [http://dx.doi.org/10.4046/trd.2012.73.1.11] [PMID: 23101020]

[97]
Dempke WCM, Fenchel K, Dale SP. Programmed cell death ligand-1 (PD-L1) as a biomarker for non-small cell lung cancer (NSCLC) treatment—are we barking up the wrong tree? Transl Lung Cancer Res  2018; 7(S3): S275-9.
 [http://dx.doi.org/10.21037/tlcr.2018.04.18] [PMID: 30393621]

[98]
Lee RC, Feinbaum RL, Ambros V. The C. elegans hetero-chronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell  1993; 75(5): 843-54.
 [http://dx.doi.org/10.1016/0092-8674(93)90529-Y] [PMID: 8252621]

[99]
Takamizawa J, Konishi H, Yanagisawa K, et al. Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res  2004; 64(11): 3753-6.
 [http://dx.doi.org/10.1158/0008-5472.CAN-04-0637] [PMID: 15172979]

[100]
Ruvkun G, Wightman B, Ha I. The 20 years it took to recognize the importance of tiny RNAs. Cell  2004; 116(S2): S93-6.
 [http://dx.doi.org/10.1016/S0092-8674(04)00034-0]

[101]
Souza CP, Cinegaglia NC, Felix TF, et al. Deregulated microRNAs are associated with patient survival and predicted to target genes that modulate lung cancer signaling pathways. Cancers  2020; 12(9): 2711.
 [http://dx.doi.org/10.3390/cancers12092711] [PMID: 32971741]

[102]
Boeri M, Verri C, Conte D, et al. MicroRNA signatures in tissues and plasma predict development and prognosis of computed tomography detected lung cancer. Proc Natl Acad Sci  2011; 108(9): 3713-8.
 [http://dx.doi.org/10.1073/pnas.1100048108] [PMID: 21300873]

[103]
Yuan Y, Liao H, Pu Q, et al. miR-410 induces both epithelial–mesenchymal transition and radioresistance through activation of the PI3K/mTOR pathway in non-small cell lung cancer. Signal Transduct Target Ther  2020; 5(1): 85.
 [http://dx.doi.org/10.1038/s41392-020-0182-2] [PMID: 32528035]

[104]
Pandey M, Mukhopadhyay A, Sharawat SK, Kumar S. Role of microRNAs in regulating cell proliferation, metastasis and chemoresistance and their applications as cancer biomarkers in small cell lung cancer. Biochim Biophys Acta Rev Cancer  2021; 1876(1): 188552.
 [http://dx.doi.org/10.1016/j.bbcan.2021.188552] [PMID: 33892053]

[105]
Chae DK, Park J, Cho M, et al. MiR‐195 and miR‐497 suppress tumorigenesis in lung cancer by inhibiting SMURF2‐induced TGF‐β receptor I ubiquitination. Mol Oncol  2019; 13(12): 2663-78.
 [http://dx.doi.org/10.1002/1878-0261.12581] [PMID: 31581360]

[106]
Huang X, Xiao S, Zhu X, et al. miR-196b-5p-mediated downregulation of FAS promotes NSCLC progression by activating IL6-STAT3 signaling. Cell Death Dis  2020; 11(9): 785.
 [http://dx.doi.org/10.1038/s41419-020-02997-7] [PMID: 32963220]

[107]
Zou P, Zhu M, Lian C, et al. miR-192-5p suppresses the progression of lung cancer bone metastasis by targeting TRIM44. Sci Rep  2019; 9(1): 19619.
 [http://dx.doi.org/10.1038/s41598-019-56018-5] [PMID: 31873114]

[108]
Hanna J, Hossain GS, Kocerha J. The potential for microRNA therapeutics and clinical research. Front Genet  2019; 10: 478.
 [http://dx.doi.org/10.3389/fgene.2019.00478] [PMID: 31156715]

[109]
Zhang J, Hua X, Qi N, et al. MiR-27b suppresses epithelial–mesenchymal transition and chemoresistance in lung cancer by targeting Snail1. Life Sci  2020; 254: 117238.
 [http://dx.doi.org/10.1016/j.lfs.2019.117238] [PMID: 31887300]

[110]
Pal AS, Bains M, Agredo A, Kasinski AL. Identification of microRNAs that promote erlotinib resistance in non-small cell lung cancer. Biochem Pharmacol  2021; 189: 114154.
 [http://dx.doi.org/10.1016/j.bcp.2020.114154] [PMID: 32681833]

[111]
Sun H, Sun Y. Lidocaine inhibits proliferation and metastasis of lung cancer cell via regulation of miR-539/EGFR axis. Artif Cells Nanomed Biotechnol  2019; 47(1): 2866-74.
 [http://dx.doi.org/10.1080/21691401.2019.1636807] [PMID: 31299862]

[112]
Saleh RO, Al-Ouqaili MTS, Ali E, et al. lncRNA-microRNA axis in cancer drug resistance: Particular focus on signaling pathways. Med Oncol  2024; 41(2): 52.
 [http://dx.doi.org/10.1007/s12032-023-02263-8] [PMID: 38195957]

[113]
Chen L, Xie Y, Yu M, Gou Q. Long noncoding RNAs in lung cancer: From disease markers to treatment roles. Cancer Manag Res  2022; 14: 1771-82.
 [http://dx.doi.org/10.2147/CMAR.S365762] [PMID: 35634537]

[114]
Gong WJ, Yin JY, Li XP, et al. Association of well-characterized lung cancer lncRNA polymorphisms with lung cancer susceptibility and platinum-based chemotherapy response. Tumour Biol  2016; 37(6): 8349-58.
 [http://dx.doi.org/10.1007/s13277-015-4497-5] [PMID: 26729200]

[115]
Gong W, Peng J, Yin J, et al. Association between well-characterized lung cancer lncRNA polymorphisms and platinum-based chemotherapy toxicity in Chinese patients with lung cancer. Acta Pharmacol Sin  2017; 38(4): 581-90.
 [http://dx.doi.org/10.1038/aps.2016.164] [PMID: 28260796]

[116]
Kos A, Dijkema R, Arnberg AC, van der Meide PH, Schelle-kens H. The hepatitis delta (δ) virus possesses a circular RNA. Nature  1986; 323(6088): 558-60.
 [http://dx.doi.org/10.1038/323558a0] [PMID: 2429192]

[117]
Chen HH, Zhang TN, Wu QJ, Huang XM, Zhao YH. Circular RNAs in lung cancer: Recent advances and future perspec-tives. Front Oncol  2021; 11: 664290.
 [http://dx.doi.org/10.3389/fonc.2021.664290] [PMID: 34295810]

[118]
 Oracle. Lifecycle of machine learning models. 2021. Available from: https://www.oracle.com/a/ocom/docs/data-science-lifecycle-ebook.pdf

[119]
Bie F, Qu X, Yang X, et al. Appropriate surgical modalities for stages T2a and T2b in the eighth TNM classification of lung cancer. Sci Rep  2017; 7(1): 13050.
 [http://dx.doi.org/10.1038/s41598-017-13495-w] [PMID: 29026165]

[120]
Raman V, Yang CFJ, Deng JZ, D’Amico TA. Surgical treatment for early stage non-small cell lung cancer. J Thorac Dis  2018; 10(S7): S898-904.
 [http://dx.doi.org/10.21037/jtd.2018.01.172] [PMID: 29780636]

[121]
Tandberg DJ, Tong BC, Ackerson BG, Kelsey CR. Surgery versus stereotactic body radiation therapy for stage I non–small cell lung cancer: A comprehensive review. Cancer  2018; 124(4): 667-78.
 [http://dx.doi.org/10.1002/cncr.31196] [PMID: 29266226]

[122]
Nagasaka M, Gadgeel SM. Role of chemotherapy and targeted therapy in early-stage non-small cell lung cancer. Expert Rev Anticancer Ther  2018; 18(1): 63-70.
 [http://dx.doi.org/10.1080/14737140.2018.1409624] [PMID: 29168933]

[123]
Reck M, Remon J, Hellmann MD. First-line immunotherapy for non–small-cell lung cancer. J Clin Oncol  2022; 40(6): 586-97.
 [http://dx.doi.org/10.1200/JCO.21.01497] [PMID: 34985920]

[124]
Planchard D, Popat S, Kerr K, et al. Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol  2018; 29(S4): iv192-237.
 [http://dx.doi.org/10.1093/annonc/mdy275] [PMID: 30285222]

[125]
Pua BB, Dou E, O’Connor K, Crawford CB. Integrating smoking cessation into lung cancer screening programs. Clin Imaging  2016; 40(2): 302-6.
 [http://dx.doi.org/10.1016/j.clinimag.2015.05.004] [PMID: 26088006]

[126]
Avancini A, Sartori G, Gkountakos A, et al. Physical activity and exercise in lung cancer care: Will promises be fulfilled? Oncologist  2020; 25(3): e555-69.
 [http://dx.doi.org/10.1634/theoncologist.2019-0463] [PMID: 32162811]

[127]
Wei X, Zhu C, Ji M, et al. Diet and risk of incident lung cancer: A large prospective cohort study in UK Biobank. Am J Clin Nutr  2021; 114(6): 2043-51.
 [http://dx.doi.org/10.1093/ajcn/nqab298] [PMID: 34582556]

[128]
Abdulrazaq ZA, Al-O SMT, Talib NM. Association between circulating 25-hydroxy vitamin D receptor and molecular response in multiple myeloma. Pak J Biol Sci  2023; 26(9): 472-81.
 [http://dx.doi.org/10.3923/pjbs.2023.472.481] [PMID: 38044697]

[129]
Abdulrazaq ZA, Ouqaili AMTS, Talib NM. The impact of circulating 25-hydroxyvitamin D and vitamin D receptor variation on leukemia-lymphoma outcome: Molecular and cytogenetic study. Saudi J Biol Sci  2024; 31(1): 103882.
 [http://dx.doi.org/10.1016/j.sjbs.2023.103882] [PMID: 38125732]
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DOI https://dx.doi.org/10.2174/0118756921301200240427053840	Print ISSN 1875-6921
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Current Pharmacogenomics and Personalized Medicine

Evolving Strategies in NSCLC Care: Targeted Therapies, Biomarkers, Predictive Models, and Patient Management

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