Targeted EGFR Nanotherapy in Non-Small Cell Lung Cancer
Source abstract
Abstract
Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide. Despite advances in treatment, the prognosis remains poor, highlighting the need for novel therapeutic strategies. The present review explores the potential of targeted epidermal growth factor receptor (EGFR) nanotherapy as an alternative treatment for NSCLC, showing that EGFR-targeted nanoparticles are efficiently taken up by NSCLC cells, leading to a significant reduction in tumor growth in mouse models. Consequently, we suggest that targeted EGFR nanotherapy could be an innovative treatment strategy for NSCLC; however, further studies are needed to optimize the nanoparticles and evaluate their safety and efficacy in clinical settings and human trials.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Lung Cancer Treatments and Mutations · Lung Cancer Research Studies · Lung Cancer Diagnosis and Treatment
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Department of Molecular Sciences, University of Medicine and Pharmacy “Iuliu Hațieganu”, 400349 Cluj-Napoca, Romania
Department of Morphological Sciences, University of Medicine and Pharmacy “Iuliu Hațieganu”, 400349 Cluj-Napoca, Romania
Department of Internal Medicine, University of Medicine and Pharmacy “Victor Babeș”, 300041 Timișoara, Romania
Faculty of Medicine, University of Medicine and Pharmacy “Iuliu Hațieganu”, 400349 Cluj-Napoca, Romania
Department of Microbiology, University of Medicine, Pharmacy, Science and Technology “George Emil Palade”, 540142 Târgu-Mureș, Romania
Funding
Increasing the Performance of Scientific Research, Supporting Excellence in Medical Research and Innovation
References (100+)
Show source-provided references
1. Epidemiology of Lung Cancer
2. Tobacco Smoking and Lung Cancer: Perception-Changing Facts10.12816/0003255 ↗
3. (2020). International Agency for Research on Cancer Lung Cancer Today, Globocan 2020.
4. (2023, May 01). NHS UK Lung Cancer. Available online: https://www.nhs.uk/conditions/lung-cancer/.
5. The Genomic Landscape of Young and Old Lung Cancer Patients Highlights Age-Dependent Mutation Frequencies and Clinical Actionability in Young Patients10.1002/ijc.33583 ↗
6. Lung Cancer Incidence in Young Women vs. Young Men: A Systematic Analysis in 40 Countries10.1002/ijc.32809 ↗
7. Gender and Lung Cancer-SEER-Based Analysis10.1016/j.annepidem.2020.04.003 ↗
8. (2023, May 01). Cancer of the Lung and Bronchus—Cancer Stat Facts, Available online: https://seer.cancer.gov/statfacts/html/lungb.html.
9. Early Diagnosis of Lung Cancer: Which Is the Optimal Choice?10.18632/aging.202504 ↗
10. Cassim, S., Chepulis, L., Keenan, R., Kidd, J., Firth, M., and Lawrenson, R. (2019). Patient and Carer Perceived Barriers to Early Presentation and Diagnosis of Lung Cancer: A Systematic Review. BMC Cancer, 19.10.1186/s12885-018-5169-9 ↗
11. Progress and Prospects of Early Detection in Lung Cancer10.1098/rsob.170070 ↗
12. Casagrande, G.M.S., Silva, M.O., Reis, R.M., and Leal, L.F. (2023). Liquid Biopsy for Lung Cancer: Up-to-Date and Perspectives for Screening Programs. Int. J. Mol. Sci., 24.10.3390/ijms24032505 ↗
13. Dama, E., Colangelo, T., and Fina, E. (2021). Biomarkers and Lung Cancer Early Detection: State of the Art. Cancers, 13.10.3390/cancers13153919 ↗
14. Veronesi, G., Baldwin, D.R., Henschke, C.I., Ghislandi, S., Iavicoli, S., Oudkerk, M., Koning, H.J., Shemesh, J., Field, J.K., and Zulueta, J.J. (2020). Recommendations for Implementing Lung Cancer Screening with Low-Dose Computed Tomography in Europe. Cancers, 12.10.3390/cancers12061672 ↗
15. Magnetic Particle Targeting for Diagnosis and Therapy of Lung Cancers10.1016/j.jconrel.2020.09.017 ↗
16. Early Diagnosis of Lung Cancer Using Magnetic Nanoparticles-Integrated Systems10.1515/ntrev-2022-0032 ↗
17. Small-Cell Lung Cancer10.1038/s41572-020-00235-0 ↗
18. ALDH2 as a Potential Stem Cell-Related Biomarker in Lung Adenocarcinoma: Comprehensive Multi-Omics Analysis10.1016/j.csbj.2023.02.045 ↗
19. Spectrum of Lung Adenocarcinoma10.1053/j.sult.2018.11.009 ↗
20. Squamous Cell Lung Cancer: From Tumor Genomics to Cancer Therapeutics10.1158/1078-0432.CCR-14-3039 ↗
21. Squamous Cell Carcinoma of the Lung10.1177/2374289517705950 ↗
22. Kini, S.R. (2002). Color Atlas of Pulmonary Cytopathology, Springer.10.1007/978-0-387-21641-6 ↗
23. Clinical Characteristics, and Treatments of Large Cell Lung Carcinoma: A Retrospective Study Using SEER Data10.21037/tcr.2020.01.40 ↗
24. Treatment for Small Cell Lung Cancer, Where Are We Now?—A Review
25. Emerging Therapies for Small Cell Lung Cancer10.1186/s13045-019-0736-3 ↗
26. Molecular Biology of Lung Cancer: Clinical Implications10.1016/j.ccm.2011.08.003 ↗
27. Andrini, E., Marchese, P.V., and Biase, D. (2022). Large Cell Neuroendocrine Carcinoma of the Lung: Current Understanding and Challenges. J. Clin. Med., 11.10.3390/jcm11051461 ↗
28. Simbolo, M., Centonze, G., Giudice, L., Grillo, F., Maisonneuve, P., Gkountakos, A., Ciaparrone, C., Cattaneo, L., Sabella, G., and Giugno, R. (2022). Combined Large Cell Neuroendocrine Carcinomas of the Lung: Integrative Molecular Analysis Identifies Subtypes with Potential Therapeutic Implications. Cancers, 14.10.3390/cancers14194653 ↗
29. Cancer Progress and Priorities: Lung Cancer10.1158/1055-9965.EPI-19-0221 ↗
30. Inhibition of DHHC20-Mediated EGFR Palmitoylation Creates a Dependence on EGFR Signaling10.1016/j.molcel.2016.04.003 ↗
31. Amphiregulin Induces Tyrosine Phosphorylation of the Epidermal Growth Factor. Receptor and P185erbB2. Evidence That Amphiregulin Acts Exclusively through the Epidermal Growth Factor Receptor at the Surface of Human Epithelial Cells10.1016/S0021-9258(18)53862-X ↗
32. Functional Independence of the Epidermal Growth Factor Receptor from a Domain Required for Ligand-Induced Internalization and Calcium Regulation10.1016/0092-8674(89)90867-2 ↗
33. Class II Phosphoinositide 3-Kinases Are Downstream Targets of Activated Polypeptide Growth Factor Receptors10.1128/MCB.20.11.3817-3830.2000 ↗
34. Jurišić, V., Obradovic, J., Pavlović, S., and Djordjevic, N. (2018). Epidermal Growth Factor Receptor Gene in Non-Small-Cell Lung Cancer: The Importance of Promoter Polymorphism Investigation. Anal. Cell. Pathol., 6192187.10.1155/2018/6192187 ↗
35. Karlsen, E.-A., Kahler, S., Tefay, J., Joseph, S.R., and Simpson, F. (2021). Epidermal Growth Factor Receptor Expression and Resistance Patterns to Targeted Therapy in Non-Small Cell Lung Cancer: A Review. Cells, 10.10.3390/cells10051206 ↗
36. UniProt Consortium (2021). UniProt: The Universal Protein Knowledgebase in 2021. Nucleic Acids Res., 49, D480–D489.
37. Characterization of Monoclonal Antibodies Generated to the 287–302 Amino Acid Loop of the Human Epidermal Growth Factor Receptor
38. Mechanisms of Activation of Receptor Tyrosine Kinases: Monomers or Dimers10.3390/cells3020304 ↗
39. A Comprehensive Pathway Map of Epidermal Growth Factor Receptor Signaling10.1038/msb4100014 ↗
40. Targeting the MAPK-RAS-RAF Signaling Pathway in Cancer Therapy10.1517/14728222.2011.645805 ↗
41. Wee, P., and Wang, Z. (2017). Epidermal Growth Factor Receptor Cell Proliferation Signaling Pathways. Cancers, 9.10.3390/cancers9050052 ↗
42. Targeting the EGFR Signaling Pathway in Cancer Therapy10.1517/14728222.2011.648617 ↗
43. Targeting EGFR-Mediated Autophagy as a Potential Strategy for Cancer Therapy10.1002/ijc.31398 ↗
44. EGFR and NF-ΚB: Partners in Cancer10.1016/j.molmed.2015.04.001 ↗
45. Epithelial Inflammation Resulting from an Inherited Loss-of-Function Mutation in EGFR10.1038/jid.2014.164 ↗
46. The Epidermal Growth Factor Receptor Variant III (EGFRvIII): Where Wild Things Are Altered10.1111/febs.12393 ↗
47. Epidermal Growth Factor Receptor and EGFRvIII in Glioblastoma: Signaling Pathways and Targeted Therapies10.1038/s41388-017-0045-7 ↗
48. The EGFR Variant III Mutant as a Target for Immunotherapy of Glioblastoma Multiforme10.1016/j.ejphar.2017.05.064 ↗
49. Amplification and Expression of the Epidermal Growth Factor Receptor Gene in Human Glioma Xenografts
50. A Deletion Mutation within the Ligand Binding Domain Is Responsible for Activation of Epidermal Growth Factor Receptor Gene in Human Brain Tumors10.1111/j.1349-7006.1990.tb02644.x ↗
51. Differential Gene Expression Analysis Reveals Generation of an Autocrine Loop by a Mutant Epidermal Growth Factor Receptor in Glioma Cells10.1158/0008-5472.CAN-05-2753 ↗
52. Rutkowska, A., Stoczyńska-Fidelus, E., Janik, K., Włodarczyk, A., and Rieske, P. (2019). EGFRvIII: An Oncogene with Ambiguous Role. J. Oncol., 1092587.10.1155/2019/1092587 ↗
53. The Plasticity of Oncogene Addiction: Implications for Targeted Therapies Directed to Receptor Tyrosine Kinases10.1593/neo.09230 ↗
54. The AMPK Agonist AICAR Inhibits the Growth of EGFRvIII-Expressing Glioblastomas by Inhibiting Lipogenesis10.1073/pnas.0906606106 ↗
55. Increased Lipogenesis in Cancer Cells: New Players, Novel Targets10.1097/01.mco.0000232894.28674.30 ↗
56. Bagheri, S., Rahban, M., Bostanian, F., Esmaeilzadeh, F., Bagherabadi, A., Zolghadri, S., and Stanek, A. (2022). Targeting Protein Kinases and Epigenetic Control as Combinatorial Therapy Options for Advanced Prostate Cancer Treatment. Pharmaceutics, 14.10.3390/pharmaceutics14030515 ↗
57. Metabolic Rewiring in Glioblastoma Cancer: EGFR, IDH and Beyond10.3389/fonc.2022.901951 ↗
58. Epidermal Growth Factor Receptor Variant III Mutations in Lung Tumorigenesis and Sensitivity to Tyrosine Kinase Inhibitors10.1073/pnas.0510284103 ↗
59. Development of a Real-Time RT-PCR Assay for Detecting EGFRvIII in Glioblastoma Samples10.1158/1078-0432.CCR-07-1966 ↗
60. Amelia, T., Kartasasmita, R.E., Ohwada, T., and Tjahjono, D.H. (2022). Structural Insight and Development of EGFR Tyrosine Kinase Inhibitors. Molecules, 27.10.3390/molecules27030819 ↗
61. Overview of Epidermal Growth Factor Receptor Biology and Its Role as a Therapeutic Target in Human Neoplasia10.1053/sonc.2002.35642 ↗
62. (2017). AACR Project GENIE Consortium AACR Project GENIE: Powering Precision Medicine through an International Consortium. Cancer Discov., 7, 818–831.
63. Activating Mutations in the Epidermal Growth Factor Receptor Underlying Responsiveness of Non-Small-Cell Lung Cancer to Gefitinib10.1056/NEJMoa040938 ↗
64. Determining the Appropriate Treatment for Different EGFR Mutations in Non-Small Cell Lung Cancer Patients10.1080/17476348.2020.1746646 ↗
65. Treatment of Non-Small Cell Lung Cancer with EGFR-Mutations10.7888/juoeh.41.153 ↗
66. Determining EGFR-TKI Sensitivity of G719X and Other Uncommon EGFR Mutations in Non-Small Cell Lung Cancer. Perplexity Solut10.3892/or.2017.5409 ↗
67. Multiplex Picoliter-Droplet Digital PCR for Quantitative Assessment of EGFR Mutations in Circulating Cell-Free DNA Derived from Advanced Non-Small Cell Lung Cancer Patients10.3892/mmr.2017.6712 ↗
68. Ulivi, P., Petracci, E., Canale, M., Priano, I., Capelli, L., Calistri, D., Chiadini, E., Cravero, P., Rossi, A., and Delmonte, A. (2021). Liquid Biopsy for EGFR Mutation Analysis in Advanced Non-Small-Cell Lung Cancer Patients: Thoughts Drawn from a Real-Life Experience. Biomedicines, 9.10.3390/biomedicines9101299 ↗
69. Plasma-Based Early Screening and Monitoring of EGFR Mutations in NSCLC Patients by a 3-Color Digital PCR Assay10.1038/s41416-020-1024-2 ↗
70. Santaniello, A., Napolitano, F., Servetto, A., De Placido, P., Silvestris, N., Bianco, C., Formisano, L., and Bianco, R. (2019). Tumour Microenvironment and Immune Evasion in EGFR Addicted NSCLC: Hurdles and Possibilities. Cancers, 11.10.3390/cancers11101419 ↗
71. (2023, May 01). Lung Cancer Statistics|How Common Is Lung Cancer?. Available online: https://www.cancer.org/cancer/lung-cancer/about/key-statistics.html.
72. (2023, May 01). Lung Cancer Survival Rates|5-Year Survival Rates for Lung Cancer. Available online: https://www.cancer.org/cancer/lung-cancer/detection-diagnosis-staging/survival-rates.html.
73. (2023, May 01). Lung Cancer—Non-Small Cell—Types of Treatment. Available online: https://www.cancer.net/cancer-types/lung-cancer-non-small-cell/types-treatment.
74. (2023, May 01). Lung Cancer—Non-Small Cell—Stages. Available online: https://www.cancer.net/cancer-types/lung-cancer-non-small-cell/stages.
75. Novel Treatment Strategies for Early-Stage Lung Cancer: The Oncologist’s Perspective10.21037/jtd.2020.02.46 ↗
76. Is Surgery Still. the Best. Management Option for Early Stage NSCLC?
77. Alternatives to Surgery for Early Stage Non-Small Cell Lung Cancer-Ready for Prime Time?10.1007/s11864-010-0119-z ↗
78. Randomized Trial of Lobectomy versus Limited Resection for T1N0 Non-Small Cell Lung Cancer
79. Lung Adjuvant Cisplatin Evaluation: A Pooled Analysis by the LACE Collaborative Group10.1200/JCO.2007.13.9030 ↗
80. Early and Locally Advanced Non-Small-Cell Lung Cancer (NSCLC): ESMO Clinical Practice Guidelines for Diagnosis, Treatment and Follow-Up10.1093/annonc/mdx222 ↗
81. (2023, May 01). Non-Small Cell Lung Cancer Treatment by Stage. Available online: https://www.cancer.org/cancer/lung-cancer/treating-non-small-cell/by-stage.html.
82. Management of Stage III Non-Small-Cell Lung Cancer: ASCO Guideline10.1200/JCO.21.02528 ↗
83. Concomitant Radio-Chemotherapy Based on Platin Compounds in Patients with Locally Advanced Non-Small Cell Lung Cancer (NSCLC): A Meta-Analysis of Individual Data from 1764 Patients10.1093/annonc/mdj117 ↗
84. Tecemotide (L-BLP25) versus Placebo after Chemoradiotherapy for Stage III Non-Small-Cell Lung Cancer (START): A Randomised, Double-Blind, Phase 3 Trial10.1016/S1470-2045(13)70510-2 ↗
85. Standard-Dose versus High-Dose Conformal Radiotherapy with Concurrent and Consolidation Carboplatin plus Paclitaxel with or without Cetuximab for Patients with Stage IIIA or IIIB Non-Small-Cell Lung Cancer (RTOG 0617): A Randomised, Two-by-Two Factorial Phase 3 Study10.1016/S1470-2045(14)71207-0 ↗
86. Metastatic Non-Small Cell Lung Cancer: ESMO Clinical Practice Guidelines for Diagnosis, Treatment and Follow-Up10.1093/annonc/mdy275 ↗
87. First-Line Therapies for Metastatic Lung Adenocarcinoma without a Driver Mutation10.1200/JOP.18.00250 ↗
88. König, D., Savic Prince, S., and Rothschild, S.I. (2021). Targeted Therapy in Advanced and Metastatic Non-Small Cell Lung Cancer. An Update on Treatment of the Most Important Actionable Oncogenic Driver Alterations. Cancers, 13.10.3390/cancers13040804 ↗
89. Treatment of Recurrent Disease in Lung Cancer10.1002/ssu.10029 ↗
90. Pembrolizumab for the Treatment of Non-Small-Cell Lung Cancer10.1056/NEJMoa1501824 ↗
91. Nivolumab versus Docetaxel in Advanced Squamous-Cell Non–Small-Cell Lung Cancer10.1056/NEJMoa1504627 ↗
92. Palliative Radiotherapy Regimens for Non-Small Cell Lung Cancer
93. Current Landscape of Palliative Radiotherapy for Non-Small-Cell Lung Cancer10.21037/tlcr.2019.08.10 ↗
94. Overcoming Therapy Resistance in EGFR-Mutant Lung Cancer10.1038/s43018-021-00195-8 ↗
95. Emerging Functions of the EGFR in Cancer10.1002/1878-0261.12155 ↗
96. Epidermal Growth Factor Receptor (EGFR) in Lung Cancer: An Overview and Update
97. Chhouri, H., Alexandre, D., and Grumolato, L. (2023). Mechanisms of Acquired Resistance and Tolerance to EGFR Targeted Therapy in Non-Small Cell Lung Cancer. Cancers, 15.10.3390/cancers15020504 ↗
98. Advances on EGFR Mutation for Lung Cancer
99. Mechanisms of Resistance to EGFR Tyrosine Kinase Inhibitors10.1016/j.apsb.2015.07.001 ↗
100. The Allelic Context of the C797S Mutation Acquired upon Treatment with Third-Generation EGFR Inhibitors Impacts Sensitivity to Subsequent Treatment Strategies10.1158/1078-0432.CCR-15-0560 ↗