Exploration of Targeted Anti-tumor Therapy

Table 1. Representative nanotechnology strategies to overcome drug resistance in lung cancer.

Strategy	Nanoplatform	Model	Study type	Key outcome	Reference
Ferroptosis-inducing	Ball-rod Janus NP (Fe³⁺/GOx/Sorafenib)	A549 NSCLC xenograft	Preclinical	GPX4 suppression + ROS ↑ → tumor inhibition in sorafenib-resistant lung tumors	[80]
Ferroptosis-inducing	FePt@HA NP (targeting CD44)	EGFR-TKI-resistant mesenchymal NSCLC	Preclinical	Ferroptosis in erlotinib-resistant EMT-NSCLC cells	[81]
CRISPR via nanocarriers	HA liposome/protamine + Cas9-MTH1	NSCLC (A549); liver metastasis mice	Preclinical	MTH1 knockout → reduced lung tumor + liver mets	[82]
	C14-PEG-PEI micelleplex (Cas9-KRAS G12S)	KRAS-mutant NSCLC (A549)	Preclinical	KRAS editing → cell death ↑, migration ↓	[83]
	Cryo-shocked tumor vesicle (Cas9-CDK4)	KRAS-driven NSCLC mice	Preclinical	CDK4 knockout → regression + survival benefit	[84]
Reformulated nano-chemotherapy	Inhalable liposome (osimertinib + IGF2BP3-plasmid)	EGFR⁺ NSCLC + brain mets (mouse)	Preclinical	Dual lung/brain targeting → tumor & brain mets suppression	[85]
	PEG-polymer NP (cisplatin + fluvastatin)	TP53-mutant NSCLC (H1975)	Preclinical	Mutant p53 degradation → restored cisplatin sensitivity	[86]
	Cetuximab-chitosan NP (PTX + quercetin)	A549/Taxol-resistant model	Preclinical	P-gp bypassed → paclitaxel re-sensitization	[87]
ADCs	Telisotuzumab vedotin (anti-c-MET-MMAE)	EGFR-TKI-resistant NSCLC (high c-MET)	Early clinical	ORR 50% + PFS benefit with osimertinib in TKI-resistant c-MET + NSCLC	[88]
	DB-1314 (anti-DLL3-topoisomerase inhibitor)	Drug-resistant SCLC (PDX & cell lines)	Preclinical	DLL3 ADC reversed platinum resistance, durable tumor regression	[89]
	Tusamitamab ravtansine (anti-CEACAM5-DM4)	Heavily pretreated CEACAM5-high NSCLC	Early clinical	ORR ~20%, durable responses in multi-drug-resistant adenocarcinoma	[90]

Return to article view

NP: nanoparticle; Gox: glucose oxidase; Fe³⁺: ferric ion; ROS: reactive oxygen species; GPX4: glutathione peroxidase 4; NSCLC: non-small cell lung cancer; EGFR-TKI: epidermal growth factor receptor-tyrosine kinase inhibitor; EMT: epithelial-mesenchymal transition; CRISPR: clustered regularly interspaced short palindromic repeats; HA: hyaluronic acid; MTH1: MutT homolog 1; PEG: polyethylene glycol; PEI: polyethylenimine; KRAS: Kirsten rat sarcoma viral oncogene; CDK4: cyclin-dependent kinase 4; IGF2BP3: insulin-like growth factor 2 mRNA-binding protein 3; PTX: paclitaxel; P-gp: P-glycoprotein; ADCs: antibody-drug conjugates; MET: mesenchymal-epithelial transition; MMAE: monomethyl auristatin E; ORR: objective response rate; PFS: progression-free survival; DLL3: delta-like ligand 3; PDX: patient-derived xenograft; SCLC: small cell lung cancer; CEACAM5: carcinoembryonic antigen-related cell adhesion molecule 5; DM4: maytansinoid DM4.

Declarations

Author contributions

HL: Conceptualization, Investigation, Writing—original draft, Supervision. KS: Conceptualization, Investigation, Writing—review & editing. JL: Data curation, Validation, Visualization. All authors read and approved the submitted version.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

Not applicable.

Copyright

Publisher’s note

Open Exploration maintains a neutral stance on jurisdictional claims in published institutional affiliations and maps. All opinions expressed in this article are the personal views of the author(s) and do not represent the stance of the editorial team or the publisher.

References

Global cancer burden growing, amidst mounting need for services [Internet]. WHO; c2025 [cited 2024 Feb 1]. Available from: https://www.who.int/news/item/01-02-2024-global-cancer-burden-growing--amidst-mounting-need-for-services

Mengistu BA, Tsegaw T, Demessie Y, Getnet K, Bitew AB, Kinde MZ, et al. Comprehensive review of drug resistance in mammalian cancer stem cells: implications for cancer therapy. Cancer Cell Int. 2024;24:406. [DOI] [PubMed] [PMC]

Cruz A, Barbosa J, Antunes P, Bonifácio VDB, Pinto SN. A Glimpse into Dendrimers Integration in Cancer Imaging and Theranostics. Int J Mol Sci. 2023;24:5430. [DOI] [PubMed] [PMC]

Meng W, Huang L, Guo J, Xin Q, Liu J, Hu Y. Innovative Nanomedicine Delivery: Targeting Tumor Microenvironment to Defeat Drug Resistance. Pharmaceutics. 2024;16:1549. [DOI] [PubMed] [PMC]

Chehelgerdi M, Chehelgerdi M, Allela OQB, Pecho RDC, Jayasankar N, Rao DP, et al. Progressing nanotechnology to improve targeted cancer treatment: overcoming hurdles in its clinical implementation. Mol Cancer. 2023;22:169. [DOI] [PubMed] [PMC]

Lin C, Huang X, Xue Y, Jiang S, Chen C, Liu Y, et al. Advances in medical devices using nanomaterials and nanotechnology: Innovation and regulatory science. Bioact Mater. 2025;48:353–69. [DOI] [PubMed] [PMC]

Sarma K, Akther MH, Ahmad I, Afzal O, Altamimi ASA, Alossaimi MA, et al. Adjuvant Novel Nanocarrier-Based Targeted Therapy for Lung Cancer. Molecules. 2024;29:1076. [DOI] [PubMed] [PMC]

Holder JE, Ferguson C, Oliveira E, Lodeiro C, Trim CM, Byrne LJ, et al. The use of nanoparticles for targeted drug delivery in non-small cell lung cancer. Front Oncol. 2023;13:1154318. [DOI] [PubMed] [PMC]

Tian H, Zhang T, Qin S, Huang Z, Zhou L, Shi J, et al. Enhancing the therapeutic efficacy of nanoparticles for cancer treatment using versatile targeted strategies. J Hematol Oncol. 2022;15:132. [DOI] [PubMed] [PMC]

10.

Zhang J, Lin Y, Lin Z, Wei Q, Qian J, Ruan R, et al. Stimuli-Responsive Nanoparticles for Controlled Drug Delivery in Synergistic Cancer Immunotherapy. Adv Sci (Weinh). 2022;9:e2103444. [DOI] [PubMed] [PMC]

11.

Yoneshima Y, Morita S, Ando M, Nakamura A, Iwasawa S, Yoshioka H, et al. Phase 3 Trial Comparing Nanoparticle Albumin-Bound Paclitaxel With Docetaxel for Previously Treated Advanced NSCLC. J Thorac Oncol. 2021;16:1523–32. [DOI] [PubMed]

12.

de Oliveira Cardoso VM, Bistaffa MJ, Sterman RG, de Lima LLP, Toldo GS, Cancino-Bernardi J, et al. Nanomedicine Innovations for Lung Cancer Diagnosis and Therapy. ACS Appl Mater Interfaces. 2025;17:13197–220. [DOI] [PubMed] [PMC]

13.

Arandhara A, Bhuyan P, Das BK. Exploring lung cancer microenvironment: pathways and nanoparticle-based therapies. Discov Oncol. 2025;16:159. [DOI] [PubMed] [PMC]

14.

Lim Z, Ma PC. Emerging insights of tumor heterogeneity and drug resistance mechanisms in lung cancer targeted therapy. J Hematol Oncol. 2019;12:134. [DOI] [PubMed] [PMC]

15.

Xue Y, Hou S, Ji H, Han X. Evolution from genetics to phenotype: reinterpretation of NSCLC plasticity, heterogeneity, and drug resistance. Protein Cell. 2017;8:178–90. [DOI] [PubMed] [PMC]

16.

Sriraman SK, Aryasomayajula B, Torchilin VP. Barriers to drug delivery in solid tumors. Tissue Barriers. 2014;2:e29528. [DOI] [PubMed] [PMC]

17.

Mangal S, Gao W, Li T, Zhou QT. Pulmonary delivery of nanoparticle chemotherapy for the treatment of lung cancers: challenges and opportunities. Acta Pharmacol Sin. 2017;38:782–97. [DOI] [PubMed] [PMC]

18.

Rosière R, Berghmans T, Vuyst PD, Amighi K, Wauthoz N. The Position of Inhaled Chemotherapy in the Care of Patients with Lung Tumors: Clinical Feasibility and Indications According to Recent Pharmaceutical Progresses. Cancers (Basel). 2019;11:329. [DOI] [PubMed] [PMC]

19.

Alqosaibi AI. Nanocarriers for anticancer drugs: Challenges and perspectives. Saudi J Biol Sci. 2022;29:103298. [DOI] [PubMed] [PMC]

20.

de Oliveira JV, de Rocha MCO, de Sousa-Junior AA, Rodrigues MC, Farias GR, de Silva PB, et al. Tumor vascular heterogeneity and the impact of subtumoral nanoemulsion biodistribution. Nanomedicine (Lond). 2022;17:2073–88. [DOI] [PubMed]

21.

Sharma A, Shambhwani D, Pandey S, Singh J, Lalhlenmawia H, Kumarasamy M, et al. Advances in Lung Cancer Treatment Using Nanomedicines. ACS Omega. 2022;8:10–41. [DOI] [PubMed] [PMC]

22.

Wu J. The Enhanced Permeability and Retention (EPR) Effect: The Significance of the Concept and Methods to Enhance Its Application. J Pers Med. 2021;11:771. [DOI] [PubMed] [PMC]

23.

Ara N, Hafeez A. Nanocarrier-Mediated Drug Delivery via Inhalational Route for Lung Cancer Therapy: A Systematic and Updated Review. AAPS PharmSciTech. 2024;25:47. [DOI] [PubMed]

24.

Jeon S, Jun E, Chang H, Yhee JY, Koh E, Kim Y, et al. Prediction the clinical EPR effect of nanoparticles in patient-derived xenograft models. J Control Release. 2022;351:37–49. [DOI] [PubMed]

25.

Pandey P, Arya DK, Kumar A, Kaushik A, Mishra YK, Rajinikanth PS. Dual ligand functionalized pH-sensitive liposomes for metastatic breast cancer treatment: in vitro and in vivo assessment. J Mater Chem B. 2025;13:2682–94. [DOI] [PubMed]

26.

Ezhilarasan D, Lakshmi T, Mallineni SK. Nano-based targeted drug delivery for lung cancer: therapeutic avenues and challenges. Nanomedicine (Lond). 2022;17:1855–69. [DOI] [PubMed]

27.

Ruiz A, Morais PC, de Azevedo RB, Lacava ZGM, Villanueva A, del Puerto Morales M. Magnetic nanoparticles coated with dimercaptosuccinic acid: development, characterization, and application in biomedicine. J Nanopart Res. 2014;16:2589. [DOI]

28.

Amaral AC, Bocca AL, Ribeiro AM, Nunes J, Peixoto DLG, Simioni AR, et al. Amphotericin B in poly(lactic-co-glycolic acid) (PLGA) and dimercaptosuccinic acid (DMSA) nanoparticles against paracoccidioidomycosis. J Antimicrob Chemother. 2009;63:526–33. [DOI] [PubMed]

29.

Moles E, Chang DW, Mansfeld FM, Duly A, Kimpton K, Logan A, et al. EGFR Targeting of Liposomal Doxorubicin Improves Recognition and Suppression of Non-Small Cell Lung Cancer. Int J Nanomedicine. 2024;19:3623–39. [DOI] [PubMed] [PMC]

30.

Lan X, Wang X, Shao L, An J, Rong S, Yang X, et al. Effect of Transferrin-Modified Fe₃O₄Nanoparticle Targeted Delivery miR-15a-5p Combined With Photothermal Therapy on Lung Cancer. Thorac Cancer. 2025;16:e15497. [DOI] [PubMed] [PMC]

31.

Greifenstein L, Gunkel A, Hoehne A, Osterkamp F, Smerling C, Landvogt C, et al. 3BP-3940, a highly potent FAP-targeting peptide for theranostics - production, validation and first in human experience with Ga-68 and Lu-177. iScience. 2023;26:108541. [DOI] [PubMed] [PMC]

32.

Dang BN, Duwa R, Lee S, Kwon TK, Chang J, Jeong J, et al. Targeting tumor-associated macrophages with mannosylated nanotherapeutics delivering TLR7/8 agonist enhances cancer immunotherapy. J Control Release. 2024;372:587–608. [DOI] [PubMed]

33.

Motiei M, Mišík O, Truong TH, Lizal F, Humpolíček P, Sedlařík V, et al. Engineering of inhalable nano-in-microparticles for co-delivery of small molecules and miRNAs. Discov Nano. 2023;18:38. [DOI] [PubMed] [PMC]

34.

El-Sherbiny IM, El-Baz NM, Yacoub MH. Inhaled nano- and microparticles for drug delivery. Glob Cardiol Sci Pract. 2015;2015:2. [DOI] [PubMed] [PMC]

35.

Chan HW, Zhang X, Chow S, Lam DCL, Chow SF. Inhalable paclitaxel nanoagglomerate dry powders for lung cancer chemotherapy: Design of experiments-guided development, characterization and in vitro evaluation. Int J Pharm. 2024;653:123877. [DOI] [PubMed]

36.

Kaga E, Kaga S, Altunbas K, Okumus N. Inhalable Nano Formulation of Cabazitaxel: A Comparative Study with Intravenous Route. Macromol Biosci. 2025;25:e2400567. [DOI] [PubMed] [PMC]

37.

Jeong Y, Shim YS, Jo YK, Cha HJ. Redox-activatable inhalable mucoadhesive proteinic nanotherapeutics for targeted treatment of lung cancer. Biomaterials. 2025;316:123004. [DOI] [PubMed]

38.

Fu X, Shi Y, Wu H, Zhang Y, Liu Y, Wan X, et al. Inhalable liposomal delivery of osimertinib and DNA for treating primary and metastasis lung cancer. Nat Commun. 2025;16:3336. [DOI] [PubMed] [PMC]

39.

Fatani WK, Aleanizy FS, Alqahtani FY, Alanazi MM, Aldossari AA, Shakeel F, et al. Erlotinib-Loaded Dendrimer Nanocomposites as a Targeted Lung Cancer Chemotherapy. Molecules. 2023;28:3974. [DOI] [PubMed] [PMC]

40.

Wu R, Zhang Z, Wang B, Chen G, Zhang Y, Deng H, et al. Combination Chemotherapy of Lung Cancer - Co-Delivery of Docetaxel Prodrug and Cisplatin Using Aptamer-Decorated Lipid-Polymer Hybrid Nanoparticles. Drug Des Devel Ther. 2020;14:2249–61. [DOI] [PubMed] [PMC]

41.

Daram A, Sawant SS, Mehta DA, Sanhueza CA, Kunda NK. Inhalable Anti-EGFR Antibody-Conjugated Osimertinib Liposomes for Non-Small Cell Lung Cancer. Pharmaceutics. 2024;16:1444. [DOI] [PubMed] [PMC]

42.

Ma Z, Wong SW, Forgham H, Esser L, Lai M, Leiske MN, et al. Aerosol delivery of star polymer-siRNA nanoparticles as a therapeutic strategy to inhibit lung tumor growth. Biomaterials. 2022;285:121539. [DOI] [PubMed]

43.

Wang W, Fu F, Huang Z, Wang W, Chen M, Yue X, et al. Inhalable Biomimetic Protein Corona-Mediated Nanoreactor for Self-Amplified Lung Adenocarcinoma Ferroptosis Therapy. ACS Nano. 2022;16:8370–87. [DOI] [PubMed]

44.

Gonsalves A, Sorkhdini P, Bazinet J, Ghumman M, Dhamecha D, Zhou Y, et al. Development and characterization of lung surfactant-coated polymer nanoparticles for pulmonary drug delivery. Biomater Adv. 2023;150:213430. [DOI] [PubMed] [PMC]

45.

Chen Y, Luh F, Ho Y, Yen Y. Exosomes: a review of biologic function, diagnostic and targeted therapy applications, and clinical trials. J Biomed Sci. 2024;31:67. [DOI] [PubMed] [PMC]

46.

Liu M, Hu S, Yan N, Popowski KD, Cheng K. Inhalable extracellular vesicle delivery of IL-12 mRNA to treat lung cancer and promote systemic immunity. Nat Nanotechnol. 2024;19:565–75. [DOI] [PubMed]

47.

Alvarez-Erviti L, Seow Y, Yin H, Betts C, Lakhal S, Wood MJA. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol. 2011;29:341–5. [DOI] [PubMed]

48.

Almohazey D, Ravinayagam V, Dafalla H, Balasamy RJ. Impact of pH-Responsive Cisplatin/Ribavirin-Loaded Monodispersed Magnetic Silica Nanocomposite on A549 Lung Cancer Cells. Pharmaceutics. 2025;17:631. [DOI] [PubMed] [PMC]

49.

Vaghasiya K, Ray E, Sharma A, Katare OP, Verma RK. Matrix Metalloproteinase-Responsive Mesoporous Silica Nanoparticles Cloaked with Cleavable Protein for “Self-Actuating” On-Demand Controlled Drug Delivery for Cancer Therapy. ACS Appl Bio Mater. 2020;3:4987–99. [DOI] [PubMed]

50.

Wen YH, Chen KW, Cheng YT, Yu LY, Lee YW, Lo CL. Hypoxia- and glutathione-responsive polymer nanoparticles for treating normoxic and hypoxic cancer cells. J Drug Deliv Sci Technol. 2023;89:105053. [DOI]

51.

Yin X, Cui Y, Kim RS, Stiles WR, Park SH, Wang H, et al. Image-guided drug delivery of nanotheranostics for targeted lung cancer therapy. Theranostics. 2022;12:4147–62. [DOI] [PubMed] [PMC]

52.

Verry C, Dufort S, Lemasson B, Grand S, Pietras J, Troprès I, et al. Targeting brain metastases with ultrasmall theranostic nanoparticles, a first-in-human trial from an MRI perspective. Sci Adv. 2020;6:eaay5279. [DOI] [PubMed] [PMC]

53.

Jeong HY, Kang SJ, Kim MW, Jeong I, Choi MJ, Jung C, et al. Development of PET Radioisotope Copper-64-Labeled Theranostic Immunoliposomes for EGFR Overexpressing Cancer-Targeted Therapy and Imaging. Int J Mol Sci. 2024;25:1813. [DOI] [PubMed] [PMC]

54.

Qiu C, Xia F, Tu Q, Tang H, Liu Y, Liu H, et al. Multimodal lung cancer theranostics via manganese phosphate/quercetin particle. Mol Cancer. 2025;24:43. [DOI] [PubMed] [PMC]

55.

Lu K, Pan X, Zheng J, Cheng D, Zheng L, Zhang X. Theranostic nanoparticles ZIF-8@ICG for pH/NIR-responsive drug-release and NIR-guided chemo-phototherapy against non-small-cell lung cancer. J Mater Sci Mater Med. 2024;35:32. [DOI] [PubMed] [PMC]

56.

Monge-Fuentes V, Garcia MP, Tavares MCH, Valois CRA, Lima ECD, Teixeira DS, et al. Biodistribution and biocompatibility of DMSA-stabilized maghemite magnetic nanoparticles in nonhuman primates (Cebus spp.). Nanomedicine (Lond). 2011;6:1529–44. [DOI] [PubMed]

57.

Singh SB. Discovery and Development of Dolastatin 10-Derived Antibody Drug Conjugate Anticancer Drugs. J Nat Prod. 2022;85:666–87. [DOI] [PubMed]

58.

Reda M, Ngamcherdtrakul W, Nelson MA, Siriwon N, Wang R, Zaidan HY, et al. Development of a nanoparticle-based immunotherapy targeting PD-L1 and PLK1 for lung cancer treatment. Nat Commun. 2022;13:4261. [DOI] [PubMed] [PMC]

59.

Song S, Shim MK, Yang S, Lee J, Yun WS, Cho H, et al. All-in-one glycol chitosan nanoparticles for co-delivery of doxorubicin and anti-PD-L1 peptide in cancer immunotherapy. Bioact Mater. 2023;28:358–75. [DOI] [PubMed] [PMC]

60.

Yu Y, Li J, Song B, Ma Z, Zhang Y, Sun H, et al. Polymeric PD-L1 blockade nanoparticles for cancer photothermal-immunotherapy. Biomaterials. 2022;280:121312. [DOI] [PubMed]

61.

Baljon JJ, Kwiatkowski AJ, Pagendarm HM, Stone PT, Kumar A, Bharti V, et al. A Cancer Nanovaccine for Co-Delivery of Peptide Neoantigens and Optimized Combinations of STING and TLR4 Agonists. ACS Nano. 2024;18:6845–62. [DOI] [PubMed] [PMC]

62.

Li S, Jiang S, Rahman MSU, Mei J, Wang X, Jiang J, et al. Pre-Induced ICD Membrane-Coated Carrier-Free Nanoparticles for the Personalized Lung Cancer Immunotherapy. Small Methods. 2023;7:e2201569. [DOI] [PubMed]

63.

Li Y, Fang M, Yu H, Wang X, Xue S, Jiang Z, et al. Neoantigen enriched biomimetic nanovaccine for personalized cancer immunotherapy. Nat Commun. 2025;16:4783. [DOI] [PubMed] [PMC]

64.

Horvat NK, Chocarro S, Marques O, Bauer TA, Qiu R, Diaz-Jimenez A, et al. Superparamagnetic Iron Oxide Nanoparticles Reprogram the Tumor Microenvironment and Reduce Lung Cancer Regrowth after Crizotinib Treatment. ACS Nano. 2024;18:11025–41. [DOI] [PubMed] [PMC]

65.

Zhao Y, Ni Q, Zhang W, Yu S. Progress in reeducating tumor-associated macrophages in tumor microenvironment. Discov Oncol. 2024;15:312. [DOI] [PubMed] [PMC]

66.

Peng X, Fang J, Lou C, Yang L, Shan S, Wang Z, et al. Engineered nanoparticles for precise targeted drug delivery and enhanced therapeutic efficacy in cancer immunotherapy. Acta Pharm Sin B. 2024;14:3432–56. [DOI] [PubMed] [PMC]

67.

Kim J, Kim M, Yong S, Han H, Kang S, Lahiji SF, et al. Engineering TGF-β inhibitor-encapsulated macrophage-inspired multi-functional nanoparticles for combination cancer immunotherapy. Biomater Res. 2023;27:136. [DOI] [PubMed] [PMC]

68.

Adzavon KP, Zhao W, He X, Sheng W. Ferroptosis resistance in cancer cells: nanoparticles for combination therapy as a solution. Front Pharmacol. 2024;15:1416382. [DOI] [PubMed] [PMC]

69.

Wang H, Lin S, Xie J, Chen X, Deng Y, Huang P, et al. Chondroitin sulfate nanoparticles based on co-delivery dual drug induced ferroptosis in lung cancer cells by disrupting mitochondrial oxidative homeostasis. Mater Today Bio. 2025;31:101632. [DOI] [PubMed] [PMC]

70.

Hussen BM, Najmadden ZB, Abdullah SR, Rasul MF, Mustafa SA, Ghafouri-Fard S, et al. CRISPR/Cas9 gene editing: a novel strategy for fighting drug resistance in respiratory disorders. Cell Commun Signal. 2024;22:329. [DOI] [PubMed] [PMC]

71.

Lee H, Rho W, Kim Y, Chang H, Jun B. CRISPR-Cas9 Gene Therapy: Non-Viral Delivery and Stimuli-Responsive Nanoformulations. Molecules. 2025;30:542. [DOI] [PubMed] [PMC]

72.

Xing P, Wang S, Bi M, Liu Y, Zeng J, Wang X, et al. Phase 2 dose-ranging study to evaluate the efficacy and safety of liposomal irinotecan (LY01610) as a second-line treatment for patients with relapsed small cell lung cancer. EClinicalMedicine. 2024;75:102791. [DOI] [PubMed] [PMC]

73.

Shi M, Gu A, Tu H, Huang C, Wang H, Yu Z, et al. Comparing nanoparticle polymeric micellar paclitaxel and solvent-based paclitaxel as first-line treatment of advanced non-small-cell lung cancer: an open-label, randomized, multicenter, phase III trial. Ann Oncol. 2021;32:85–96. [DOI] [PubMed]

74.

Byrne MM, Sutamtewagul G, Zeitler W, Mott SL, Zamba GKD, Kojadinovic A, et al. Phase II study of nab-paclitaxel with gemcitabine for relapsed/refractory small cell lung cancer. Front Oncol. 2024;14:1303268. [DOI] [PubMed] [PMC]

75.

Okajima D, Yasuda S, Maejima T, Karibe T, Sakurai K, Aida T, et al. Datopotamab Deruxtecan, a Novel TROP2-directed Antibody-drug Conjugate, Demonstrates Potent Antitumor Activity by Efficient Drug Delivery to Tumor Cells. Mol Cancer Ther. 2021;20:2329–40. [DOI] [PubMed] [PMC]

76.

Jänne PA, Baik C, Su W, Johnson ML, Hayashi H, Nishio M, et al. Efficacy and Safety of Patritumab Deruxtecan (HER3-DXd) in EGFR Inhibitor-Resistant, EGFR-Mutated Non-Small Cell Lung Cancer. Cancer Discov. 2022;12:74–89. [DOI] [PubMed] [PMC]

77.

Yonesaka K, Tanizaki J, Maenishi O, Haratani K, Kawakami H, Tanaka K, et al. HER3 Augmentation via Blockade of EGFR/AKT Signaling Enhances Anticancer Activity of HER3-Targeting Patritumab Deruxtecan in EGFR-Mutated Non-Small Cell Lung Cancer. Clin Cancer Res. 2022;28:390–403. [DOI] [PubMed]

78.

Buyukgolcigezli I, Tenekeci AK, Sahin IH. Opportunities and Challenges in Antibody-Drug Conjugates for Cancer Therapy: A New Era for Cancer Treatment. Cancers (Basel). 2025;17:958. [DOI] [PubMed] [PMC]

79.

Coleman N, Yap TA, Heymach JV, Meric-Bernstam F, Le X. Antibody-drug conjugates in lung cancer: dawn of a new era? NPJ Precis Oncol. 2023;7:5. [DOI] [PubMed] [PMC]

80.

Zhou Y, Du Q, Zhao Q, Zhang M, Qin X, Jiang Y, et al. A heme-regulatable chemodynamic nanodrug harnessing transcription factor Bach1 against lung cancer metastasis. J Colloid Interface Sci. 2022;610:698–708. [DOI] [PubMed]

81.

Tsai T, Wu S, Lai Y, Wang H, Hou P, Huang Y, et al. CD44-hyaluronan mediating endocytosis of iron-platinum alloy nanoparticles induces ferroptotic cell death in mesenchymal-state lung cancer cells with tyrosine kinase inhibitor resistance. Acta Biomater. 2024;186:396–410. [DOI] [PubMed]

82.

Wang Y, Tang Y, Zhao X, Huang G, Gong J, Yang S, et al. A multifunctional non-viral vector for the delivery of MTH1-targeted CRISPR/Cas9 system for non-small cell lung cancer therapy. Acta Biomater. 2022;153:481–93. [DOI] [PubMed]

83.

Chen S, Triki M, Carneiro SP, Merkel OM. A novel micelleplex for tumour-targeted delivery of CRISPR-Cas9 against KRAS-mutated lung cancer. Nanoscale. 2025;17:6604–19. [DOI] [PubMed] [PMC]

84.

Liu F, Xin M, Feng H, Zhang W, Liao Z, Sheng T, et al. Cryo-shocked tumor cells deliver CRISPR-Cas9 for lung cancer regression by synthetic lethality. Sci Adv. 2024;10:eadk8264. [DOI] [PubMed] [PMC]

85.

Shu C, Li J, Rui J, Fan D, Niu Q, Bai R, et al. Uncovering the rewired IAP-JAK regulatory axis as an immune-dependent vulnerability of LKB1-mutant lung cancer. Nat Commun. 2025;16:2324. [DOI] [PubMed] [PMC]

86.

Bi Y, Chen Q, Yang M, Xing L, Jiang H. Nanoparticles targeting mutant p53 overcome chemoresistance and tumor recurrence in non-small cell lung cancer. Nat Commun. 2024;15:2759. [DOI] [PubMed] [PMC]

87.

Wang Y, Yu H, Wang S, Gai C, Cui X, Xu Z, et al. Targeted delivery of quercetin by nanoparticles based on chitosan sensitizing paclitaxel-resistant lung cancer cells to paclitaxel. Mater Sci Eng C Mater Biol Appl. 2021;119:111442. [DOI] [PubMed]

88.

Camidge DR, Bar J, Horinouchi H, Goldman J, Moiseenko F, Filippova E, et al. Telisotuzumab Vedotin Monotherapy in Patients With Previously Treated c-Met Protein-Overexpressing Advanced Nonsquamous EGFR-Wildtype Non-Small Cell Lung Cancer in the Phase II LUMINOSITY Trial. J Clin Oncol. 2024;42:3000–11. [DOI] [PubMed] [PMC]

89.

Lin S, Zhang Y, Yao J, Yang J, Qiu Y, Zhu Z, et al. DB-1314, a novel DLL3-targeting ADC with DNA topoisomerase I inhibitor, exhibits promising safety profile and therapeutic efficacy in preclinical small cell lung cancer models. J Transl Med. 2024;22:766. [DOI] [PubMed] [PMC]

90.

Gazzah A, Bedard PL, Hierro C, Kang Y, Razak AA, Ryu M, et al. Safety, pharmacokinetics, and antitumor activity of the anti-CEACAM5-DM4 antibody-drug conjugate tusamitamab ravtansine (SAR408701) in patients with advanced solid tumors: first-in-human dose-escalation study. Ann Oncol. 2022;33:416–25. [DOI] [PubMed]

91.

Ahn M, Tanaka K, Paz-Ares L, Cornelissen R, Girard N, Pons-Tostivint E, et al.; TROPION-Lung01 Trial Investigators. Datopotamab Deruxtecan Versus Docetaxel for Previously Treated Advanced or Metastatic Non-Small Cell Lung Cancer: The Randomized, Open-Label Phase III TROPION-Lung01 Study. J Clin Oncol. 2025;43:260–72. [DOI] [PubMed] [PMC]

92.

Yu HA, Goto Y, Hayashi H, Felip E, Yang JC, Reck M, et al. HERTHENA-Lung01, a Phase II Trial of Patritumab Deruxtecan (HER3-DXd) in Epidermal Growth Factor Receptor-Mutated Non-Small-Cell Lung Cancer After Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy and Platinum-Based Chemotherapy. J Clin Oncol. 2023;41:5363–75. [DOI] [PubMed] [PMC]

93.

Li BT, Smit EF, Goto Y, Nakagawa K, Udagawa H, Mazières J, et al.; DESTINY-Lung01 Trial Investigators. Trastuzumab Deruxtecan in HER2-Mutant Non-Small-Cell Lung Cancer. N Engl J Med. 2022;386:241–51. [DOI] [PubMed] [PMC]

94.

Zhang M, Wang L, Wang Q, Yang J, Peng W, Li X, et al. Efficacy of disitamab vedotin in non-small cell lung cancer with HER2 alterations: a multicenter, retrospective real-world study. Front Oncol. 2024;14:1441025. [DOI] [PubMed] [PMC]

95.

Blackhall F, Jao K, Greillier L, Cho BC, Penkov K, Reguart N, et al. Efficacy and Safety of Rovalpituzumab Tesirine Compared With Topotecan as Second-Line Therapy in DLL3-High SCLC: Results From the Phase 3 TAHOE Study. J Thorac Oncol. 2021;16:1547–58. [DOI] [PubMed]

96.

EnGeneIC launches groundbreaking new Australian trial for innovative cancer therapy, with international trial site in Singapore to follow [Internet]. [2025 Jul 10]. Available from: https://www.globenewswire.com/news-release/2025/05/13/3079706/0/en/EnGeneIC-launches-groundbreaking-new-Australian-trial-for-innovative-cancer-therapy-with-international-trial-site-in-Singapore-to-follow.html

97.

Deme D, Öven B, Göker E, Lang I, Brück P, Wenger M, et al. 597 Preliminary results from LuCa-MERIT-1, a first-in-human Phase I trial evaluating the fixed antigen RNA vaccine BNT116 in patients with advanced non-small cell lung cancer. J Immunother Cancer. 2023;11:A679. [DOI]

98.

Atmaca A, Alt J, Baz DV, Dziadziuszko R, Moreno V, Pose V, et al. 1486 Preliminary results from LuCa-MERIT-1, a phase I trial evaluating BNT116, a fixed antigen mRNA vaccine, plus cemiplimab in advanced non-small cell lung cancer after progression on PD-1 inhibition. J Immunother Cancer. 2024;12:A1716. [DOI]

99.

Breaking Down the CONVERGE Study of NBTXR3 in Stage 3 Unresectable NSCLC [Internet]. MJH Life Sciences; c2025 [cited 2025 Jun 2]. Available from: https://www.curetoday.com/view/breaking-down-the-converge-study-of-nbtxr3-in-stage-3-unresectable-nsclc

100.

Targeted Oncology. Novel Radioenhancer JNJ-1900 Shows Potential across Cancers [Internet]. MJH Life Sciences; c2025 [cited 2025 Jul 10]. Available from: https://www.targetedonc.com/view/novel-radioenhancer-jnj-1900-shows-potential-across-cancers

101.

Spigel DR, Dowlati A, Chen Y, Navarro A, Yang JC, Stojanovic G, et al.; RESILIENT Trial Investigators. RESILIENT Part 2: A Randomized, Open-Label Phase III Study of Liposomal Irinotecan Versus Topotecan in Adults With Relapsed Small Cell Lung Cancer. J Clin Oncol. 2024;42:2317–26. [DOI] [PubMed] [PMC]

102.

Genprex Expands Gene Therapy Oncology Pipeline to Include Small Cell Lung Cancer [Internet]. [cited 2025 Jun 30]. Available from: https://www.genprex.com/genprex-expands-gene-therapy-oncology-pipeline-to-include-small-cell-lung-cancer/

103.

Lu Y, Xue J, Deng T, Zhou X, Yu K, Deng L, et al. Safety and feasibility of CRISPR-edited T cells in patients with refractory non-small-cell lung cancer. Nat Med. 2020;26:732–40. [DOI] [PubMed]

104.

Venturini J, Chakraborty A, Baysal MA, Tsimberidou AM. Developments in nanotechnology approaches for the treatment of solid tumors. Exp Hematol Oncol. 2025;14:76. [DOI] [PubMed] [PMC]

105.

Aquino VRR, Aquino JCR, Coaquira JAH, Bakuzis AF, Sousa MH, Morais PC. New synthesis route for high quality iron oxide-based nanorings: Structural and magnetothermal evaluations. Mater Des. 2023;232:112082. [DOI]

106.

Scheinberg DA, Grimm J, Heller DA, Stater EP, Bradbury M, McDevitt MR. Advances in the clinical translation of nanotechnology. Curr Opin Biotechnol. 2017;46:66–73. [DOI] [PubMed] [PMC]

107.

Li J, Wang J, Chen Z. Emerging role of exosomes in cancer therapy: progress and challenges. Mol Cancer. 2025;24:13. [DOI] [PubMed] [PMC]

108.

Dong C, Tan D, Sun H, Li Z, Zhang L, Zheng Y, et al. Interleukin-12 Delivery Strategies and Advances in Tumor Immunotherapy. Curr Issues Mol Biol. 2024;46:11548–79. [DOI] [PubMed] [PMC]

109.

Witten J, Raji I, Manan RS, Beyer E, Bartlett S, Tang Y, et al. Artificial intelligence-guided design of lipid nanoparticles for pulmonary gene therapy. Nat Biotechnol. 2024;10.1038/s41587–024–02490–y. [DOI] [PubMed]

110.

Longo JPF, Souza PENd, Morais PC. Artificial intelligence and machine learning in nanomedicine. What do we expect for 2030? Nanomedicine (Lond). 2023;18:1041–3. [DOI] [PubMed]

111.

Tan T, Li S, Hu W, Yue T, Zeng Q, Zeng X, et al. Efficacy and safety of nab-paclitaxel plus platinum in non-small cell lung cancer: a meta-analysis. Front Med (Lausanne). 2023;10:1139248. [DOI] [PubMed] [PMC]

112.

Rosenblum D, Joshi N, Tao W, Karp JM, Peer D. Progress and challenges towards targeted delivery of cancer therapeutics. Nat Commun. 2018;9:1410. [DOI] [PubMed] [PMC]