How to cite this WIREs title:
WIREs Nanomed Nanobiotechnol

Impact Factor: 7.689

A review on RNAi therapy for NSCLC: Opportunities and challenges

Advanced Review

Vignesh Kumar, Sairam Yadavilli, Raghuraman Kannan

Published Online: Nov 10 2020

DOI: 10.1002/wnan.1677

Full article on Wiley Online Library: HTML PDF

Can't access this content? Tell your librarian.

Abstract Non‐small cell lung cancer (NSCLC) is the primary cause of cancer death worldwide. Despite developments in chemotherapy and targeted therapies, the 5‐year survival rate has remained at approximately 16% for the last four decades. NSCLC is a heterogeneous group of tumors that, through mutations and drivers, also demonstrate intra‐tumor heterogeneity. Thus, current treatment approaches revolve around targeting these oncogenes, often using small molecule inhibitors and chemotherapeutics. However, the efficacy of these therapies has been crippled by acquired and inherent drug‐resistance in the tumor, accompanied by increased therapeutic dosages and subsequent devastating off‐target effects for patients. Evidently, there is a critical need for developing treatment methodologies more effective than the current standard of care. Fortunately, RNA interference, particularly small interfering RNA (siRNA), presents an alternative of silencing specific oncogenes to control tumor growth. Although siRNA therapy is subject to rapid degradation and poor internalization in vivo, nanoparticles can serve as nontoxic and efficient delivery vehicles, even introducing combinational delivery of multiple therapeutic agents. Indeed, siRNA‐nanoconstructs possess extraordinary potential as an innovative modality to address clinical needs. This state‐of‐the‐art review summarizes the recent advancements in the development of novel nanosystems for delivering siRNA to NSCLC tumors and analyzes the efficacy of representative examples. By illuminating the most promising biomarkers for silencing, we hope to streamline current therapeutic efforts and highlight powerful translational opportunities to combat NSCLC. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Biology‐Inspired Nanomaterials > Lipid‐Based Structures Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease

General classification for Type I and Type II nanosystems for siRNA delivery

[ Normal View | Magnified View ]

(a) Schematic illustration of nanoparticles containing VEGF siRNA, and etoposide for NSCLC; Evaluation of tumor growth inhibition of the nanoparticle and compared with controls in orthotopic A549 tumor models. (b) Bioluminescence images of different formulations listed in the graph at different time points—presented as days; (c) Bioluminescence image intensity of nanoparticles and combinations at predesigned time points; (d) Change in body weight of mice during treatment at different type points; (e) Representative H&E images of orthotopic A549 lung tumors after different formulations treatment. Different formulations represented (i) Saline, (ii) ETO injection, (iii) P‐Lip/ETO‐siVEGF, (iv) PHCL‐Lip/siVEGF, (v) PHCL‐Lip/ETO, (vi) PHCL‐Lip/ETO‐siVEGF. Data was represented as mean ± SD (n = 5). (Reprinted with permission from Li et al., 2019, Copyright 2020 with permission from Ivyspring)

[ Normal View | Magnified View ]

(a) Schematic illustration of synthesis of targeted [email protected] NPs; (b) Mechanism of intracellular action of [email protected] NPs carrying oncogene siRNA. (Reprinted with permission from Shi et al., 2017, Copyright 2020 with permission from American Society of Gene and Cell Therapy)

[ Normal View | Magnified View ]

Schematic illustration of (a) the in vivo codelivery mechanism and (b) the preparation procedure of GMP‐ and/or VEGF siRNA‐loaded LCP formulations. AA, anisamide; EPR, enhanced permeability and retention; GMP, gemcitabine monophosphate; LCP, lipid/calcium/phosphate. (Reprinted with permission from Zhang, Peng, et al., 2013, Copyright 2020 with permission from American Society of Gene and Cell Therapy)

[ Normal View | Magnified View ]

Results obtained using the nanoparticles in mice with human non‐small cell lung carcinoma. (a) Suppression of targeted EGFR1‐TK mRNA by siRNA delivered by non‐targeted and targeted NLC; (b) Suppression of four EGFR‐TKs by the selected pool of siRNAs delivered by targeted LHRH‐NLC‐siRNAs‐TAX system; (c) Apoptosis induction in the lung tumor; (d) Changes in lung tumor volume after beginning of treatment (mice were treated on days 0, 3, 7, 11, 14, 17, 21, and 24). The progression of tumor growth was monitored using bioluminescent and magnetic resonance imaging and tumor volume was calculated using software supplied with IVIS and magnetic resonance imaging systems. [1—Control (untreated tumor); 2—Free non‐bound TAX (I.V. administration); 3—Non‐targeted NLC‐siRNAs (inhalation); 4—Non‐targeted NLC‐TAX (inhalation); 5—Non‐targeted NLC‐siRNAs‐TAX (inhalation); 6—tumor targeted LHRH‐NLC‐siRNAs‐TAX (inhalation). Means ± SD are shown. *p < .05 when compared with control; †p < .05 when compared with free TAX; ‡p < .05 when compare with NLC‐siRNAs; +p < .05 when compared with NLC‐TAX; ×p < .05 when compared with NLC‐siRNA‐TAX]. (Reprinted with permission from Garbuzenko et al., 2019, Copyright 2020 with permission from Ivyspring)

[ Normal View | Magnified View ]

Evaluation of concurrent delivery of miR‐34a and siRNA‐Kras combination in mouse models improves therapeutic response. (a) KP cell number following incubation with 7C1‐siRNA combinations. Each siRNA dose is 30 nM. Error bars are SD (n = 3 wells per group); (b) Normalized lung tumor volume in KP mice following treatment with 7C1‐siRNA combinations. Ten weeks after tumor initiation, mice were dosed with 2 mg/kg of 7C1‐siLuc or 7C1‐miR‐34a/siKras every other day for four doses. Error bars are SD (n = 8 mice per group, n = 1 tumor per mouse). **p < .01 for 7C1‐miR‐34a/siKras compared with single treatment; (c) Quantification of apoptotic cells marked by CC3 in treated tumors (n = 27, 29, 36, and 46 tumors per time point, respectively); (d) Kaplan–Meier survival curve of KP mice treated with cisplatin and 7C1 nanoparticle formulated with miR34a/siKras combination (siCombo) therapies (n = 8, 8, 8, and 10 mice per group). Day 0 refers to tumor initiation. Arrows or arrowheads indicate time points of cisplatin or nanoparticle administration, respectively. *p < .05; **p < .01. (Reprinted with permission from Xue et al., 2014, Copyright 2020 with permission from PNAS)

[ Normal View | Magnified View ]

(a) Schematic representation of tri‐block nanoparticle (TBN) consisting of gelatin nanoparticle encapsulated with gefitinib and surface functionalized with cetuximab conjugated siRNA; (b) TEM image of Gelatin Nanoparticles; and (c) TEM image of TBN. (Reprinted with permission from Srikar et al., 2016, Copyright 2020 with permission from Nature)

[ Normal View | Magnified View ]

Evaluation of stability of nanoconstructs and transfection ability in cells. Change in hydrodynamic size of nanoconstructs in (a) water; (b) 10% serum containing RPMI media; (c) 1× PBS; and (d) change in Zeta potential for constructs in water for a duration for 120 hr. siRNA stability. (e) Stability of free‐siRNA (left) and GAbsiAXL (right) in serum was analyzed using PAGE for a duration of 48 hr. GAbsiAXL exhibits high serum stability for 48 hr while free siRNA degrades within 4 hr. No presence of unbound siRNA was detected for GAbsiAXL suggesting strong particle attachment. Gene knockdown efficacy. Change in AXL expression levels in H820 cells after 72 hr of treatment with (f) transfected siRNA; (g) nanoconstructs (with and without TKI); and (h) Downregulation efficiency of siRNA and nanoconstructs calculated by band densitometry. GAbsiAXL downregulated AXL expression successfully by over 70% (p ≤ .001; from three independent experiments). (Reprinted with permission from Suresh et al., 2019, Copyright 2020 with permission from Elsevier)

[ Normal View | Magnified View ]

Chitosan nanoparticles loaded with Mad2‐siRNA and PEG and evaluation of the nanoparticles in mice bearing A549 WT and A549 DDP xenograft tumors (a) Schematic representation of nanoparticles; (b) and percentage tumor growth inhibition following treatment with single or combination therapy of Mad2 siRNA and cisplatin in sensitive and resistant A549 tumor bearing mice n = 8 mice, **p < .01, *** p < .001 (t‐test comparing to PBS treatment). (Reprinted with permission from Nascimento et al., 2017, Copyright 2020 with permission from Elsevier)

[ Normal View | Magnified View ]

Optimizing hyaluronic acid (HA)/cisplatin nanoparticles and identifying the resistant genes in drug‐resistant cells. To determine the cisplatin resistance in resistant NSCLC cells, cisplatin drug was incubated with both sensitive and resistant cells (A549/A549^DDP) at various concentrations for 2 days. (a) Cell viability was assessed to determine the IC₅₀ (half maximal inhibitory concentration). (b) To improve the delivery, cisplatin was encapsulated in 1,8‐diaminooctane (ODA)‐modified HA nanosystems with and without poly(ethylene glycol) (PEG) and characterized. (c) The cytotoxicity of HA‐ODA and HA‐ODA/PEG nanoparticles were measured with and without cisplatin along with cisplatin alone as a control in resistant A549^DDP cells. In order to identify the resistant genes in NSCLC and SCLC cells, RNA was extracted from both resistant and sensitive cells. (d) With appropriate primers, the reverse transcription‐PCR was run to identify the expression of resistant genes. NSCLC, non‐small cell lung cancer; SCLC, small cell lung cancer. (Reprinted with permission from Ganesh et al., 2013, Copyright 2020 with permission from the American Society of Gene & Cell Therapy)

[ Normal View | Magnified View ]

Schematic illustration of synthesis of mesoporous silica nanoparticles (MSN) for an efficient targeted co‐delivery of siRNA and anticancer drugs. (a) Modification of MSN with MPTS; (b) Activation of thiol groups on the MSN surface with Aldrithiol‐2 to produced pyridyldithiol reactive groups; (c) Encapsulation of DOX inside modified MSN; (d) Encapsulation of CIS inside modified MSN; (e) Modification of surface of CIS‐loaded MSN with siRNA and PEG‐LHRH; (f) Modification of surface of DOX‐loaded MSN with siRNA and PEG‐LHRH. (Reprinted with permission from Taratula et al., 2011, Copyright 2020 with permission from Taylor & Francis)

[ Normal View | Magnified View ]

References

Ahmadzada,, T., Reid,, G., & McKenzie,, D. R. (2018). Fundamentals of siRNA and miRNA therapeutics and a review of targeted nanoparticle delivery systems in breast cancer. Biophysical Reviews, 10(1), 69–86. https://doi.org/10.1007/s12551-017-0392-1
Amreddy,, N., Babu,, A., Panneerselvam,, J., Srivastava,, A., Muralidharan,, R., Chen,, A., … Ramesh,, R. (2018). Chemo‐biologic combinatorial drug delivery using folate receptor‐targeted dendrimer nanoparticles for lung cancer treatment. Nanomedicine, 14(2), 373–384. https://doi.org/10.1016/j.nano.2017.11.010
Avastin [package insert]. U.S. Food and Drug Administration website. Retrieved from https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/125085s301lbl.pdf; 2014.
Babu,, A., Munshi,, A., & Ramesh,, R. (2017). Combinatorial therapeutic approaches with RNAi and anticancer drugs using nanodrug delivery systems. Drug Development and Industrial Pharmacy, 43(9), 1391–1401. https://doi.org/10.1080/03639045.2017.1313861
Baxevanos,, P., & Mountzios,, G. (2018). Novel chemotherapy regimens for advanced lung cancer: Have we reached a plateau? Annals of Translational Medicine, 6(8), 139. https://doi.org/10.21037/atm.2018.04.04
Beale,, P. J., Rogers,, P., Boxall,, F., Sharp,, S. Y., & Kelland,, L. R. (2000). BCL‐2 family protein expression and platinum drug resistance in ovarian carcinoma. British Journal of Cancer, 82(2), 436–440. https://doi.org/10.1054/bjoc.1999.0939
Ben Sahra,, I., Regazzetti,, C., Robert,, G., Laurent,, K., Le Marchand‐Brustel,, Y., Auberger,, P., … Bost,, F. (2011). Metformin, independent of AMPK, induces mTOR inhibition and cell‐cycle arrest through REDD1. Cancer Research, 71(13), 4366–4372. https://doi.org/10.1158/0008-5472.CAN-10-1769
Bethune,, G., Bethune,, D., Ridgway,, N., & Xu,, Z. (2010). Epidermal growth factor receptor (EGFR) in lung cancer: An overview and update. Journal of Thoracic Disease, 2(1), 48–51.
Bulbul,, A., & Husain,, H. (2018). First‐line treatment in EGFR mutant non‐small cell lung cancer: Is there a best option? Frontiers in Oncology, 8, 94. https://doi.org/10.3389/fonc.2018.00094
Chan,, B. A., & Hughes,, B. G. (2015). Targeted therapy for non‐small cell lung cancer: Current standards and the promise of the future. Translational Lung Cancer Research, 4(1), 36–54. https://doi.org/10.3978/j.issn.2218-6751.2014.05.01
Chen,, G., Kronenberger,, P., Teugels,, E., Umelo,, I. A., & De Greve,, J. (2012). Targeting the epidermal growth factor receptor in non‐small cell lung cancer cells: The effect of combining RNA interference with tyrosine kinase inhibitors or cetuximab. BMC Medicine, 10, 28. https://doi.org/10.1186/1741-7015-10-28
Chen,, X. Q., Yang,, S., Li,, Z. Y., Lu,, H. S., Kang,, M. Q., & Lin,, T. Y. (2012). Effects and mechanism of downregulation of survivin expression by RNA interference on proliferation and apoptosis of lung cancer cells. Molecular Medicine Reports, 5(4), 917–922. https://doi.org/10.3892/mmr.2012.755
Choi,, J. W., Kim,, Y., Lee,, J. H., & Kim,, Y. S. (2013). High expression of spindle assembly checkpoint proteins CDC20 and MAD2 is associated with poor prognosis in urothelial bladder cancer. Virchows Archiv: An International Journal of Pathology, 463(5), 681–687. https://doi.org/10.1007/s00428-013-1473-6
CYRAMZA [package insert]. U.S. Food and Drug Administration website. Retrieved from https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/125477s034lbl.pdf; 2020).
Di Costanzo,, F., Mazzoni,, F., Micol Mela,, M., Antonuzzo,, L., Checcacci,, D., Saggese,, M., & Di Costanzo,, F. (2008). Bevacizumab in non‐small cell lung cancer. Drugs, 68(6), 737–746. https://doi.org/10.2165/00003495-200868060-00002
Fang,, S., Wu,, L., Li,, M., Yi,, H., Gao,, G., Sheng,, Z., … Cai,, L. (2014). ZEB1 knockdown mediated using polypeptide cationic micelles inhibits metastasis and effects sensitization to a chemotherapeutic drug for cancer therapy. Nanoscale, 6(17), 10084–10094. https://doi.org/10.1039/c4nr01518e
Feng,, Y., Hu,, J., Ma,, J., Feng,, K., Zhang,, X., Yang,, S., … Zhang,, Y. (2011). RNAi‐mediated silencing of VEGF‐C inhibits non‐small cell lung cancer progression by simultaneously down‐regulating the CXCR4, CCR7, VEGFR‐2 and VEGFR‐3‐dependent axes‐induced ERK, p38 and AKT signalling pathways. European Journal of Cancer, 47(15), 2353–2363. https://doi.org/10.1016/j.ejca.2011.05.006
Fennell,, D. A., Summers,, Y., Cadranel,, J., Benepal,, T., Christoph,, D. C., Lal,, R., … Ferry,, D. (2016). Cisplatin in the modern era: The backbone of first‐line chemotherapy for non‐small cell lung cancer. Cancer Treatment Reviews, 44, 42–50. https://doi.org/10.1016/j.ctrv.2016.01.003
Gandhi,, N. S., Godeshala,, S., Koomoa‐Lange,, D. T., Miryala,, B., Rege,, K., & Chougule,, M. B. (2018). Bioreducible poly(amino ethers) based mTOR siRNA delivery for lung cancer. Pharmaceutical Research, 35(10), 188. https://doi.org/10.1007/s11095-018-2460-z
Ganesh,, S., Iyer,, A. K., Weiler,, J., Morrissey,, D. V., & Amiji,, M. M. (2013). Combination of siRNA‐directed gene silencing with Cisplatin reverses drug resistance in human non‐small cell lung cancer. Molecular Therapy ‐ Nucleic Acids, 2, e110. https://doi.org/10.1038/mtna.2013.29
Garbuzenko,, O. B., Kuzmov,, A., Taratula,, O., Pine,, S. R., & Minko,, T. (2019). Strategy to enhance lung cancer treatment by five essential elements: Inhalation delivery, nanotechnology, tumor‐receptor targeting, chemo‐ and gene therapy. Theranostics, 9(26), 8362–8376. https://doi.org/10.7150/thno.39816
Garbuzenko,, O. B., Mainelis,, G., Taratula,, O., & Minko,, T. (2014). Inhalation treatment of lung cancer: The influence of composition, size and shape of nanocarriers on their lung accumulation and retention. Cancer Biology %26 Medicine, 11(1), 44–55. https://doi.org/10.7497/j.issn.2095-3941.2014.01.004
Garbuzenko,, O. B., Saad,, M., Betigeri,, S., Zhang,, M., Vetcher,, A. A., Soldatenkov,, V. A., … Minko,, T. (2009). Intratracheal versus intravenous liposomal delivery of siRNA, antisense oligonucleotides and anticancer drug. Pharmaceutical Research, 26(2), 382–394. https://doi.org/10.1007/s11095-008-9755-4
Garbuzenko,, O. B., Saad,, M., Pozharov,, V. P., Reuhl,, K. R., Mainelis,, G., & Minko,, T. (2010). Inhibition of lung tumor growth by complex pulmonary delivery of drugs with oligonucleotides as suppressors of cellular resistance. Proceedings of the National Academy of Sciences of the United States of America, 107(23), 10737–10742. https://doi.org/10.1073/pnas.1004604107
Garg,, H., Suri,, P., Gupta,, J. C., Talwar,, G. P., & Dubey,, S. (2016). Survivin: A unique target for tumor therapy. Cancer Cell International, 16, 49. https://doi.org/10.1186/s12935-016-0326-1
Gay,, C. M., Balaji,, K., & Byers,, L. A. (2017). Giving AXL the axe: Targeting AXL in human malignancy. British Journal of Cancer, 116(4), 415–423. https://doi.org/10.1038/bjc.2016.428
Han,, H., Silverman,, J. F., Santucci,, T. S., Macherey,, R. S., d`Amato,, T. A., Tung,, M. Y., … Landreneau,, R. J. (2001). Vascular endothelial growth factor expression in stage I non‐small cell lung cancer correlates with neoangiogenesis and a poor prognosis. Annals of Surgical Oncology, 8(1), 72–79. https://doi.org/10.1007/s10434-001-0072-y
Harrison,, P. T., Vyse,, S., & Huang,, P. H. (2020). Rare epidermal growth factor receptor (EGFR) mutations in non‐small cell lung cancer. Seminars in Cancer Biology, 61, 167–179. https://doi.org/10.1016/j.semcancer.2019.09.015
Hildebrandt,, M. A., Gu,, J., & Wu,, X. (2009). Pharmacogenomics of platinum‐based chemotherapy in NSCLC. Expert Opinion on Drug Metabolism %26 Toxicology, 5(7), 745–755. https://doi.org/10.1517/17425250902973711
Hu,, B., Zhong,, L., Weng,, Y., Peng,, L., Huang,, Y., Zhao,, Y., & Liang,, X. J. (2020). Therapeutic siRNA: State of the art. Signal Transduction and Targeted Therapy, 5(1), 101. https://doi.org/10.1038/s41392-020-0207-x
Huang,, Q., Li,, L., Li,, L., Chen,, H., Dang,, Y., Zhang,, J., … Xiao,, J. (2016). MDM2 knockdown mediated by a triazine‐modified dendrimer in the treatment of non‐small cell lung cancer. Oncotarget, 7(28), 44013–44022. https://doi.org/10.18632/oncotarget.9768
Itani,, R., & Al Faraj,, A. (2019). siRNA conjugated nanoparticles‐a next generation strategy to treat lung cancer. International Journal of Molecular Sciences, 20(23), 6088‐6103. https://doi.org/10.3390/ijms20236088
Jayachandran,, G., Sazaki,, J., Nishizaki,, M., Xu,, K., Girard,, L., Minna,, J. D., … Ji,, L. (2007). Fragile histidine triad‐mediated tumor suppression of lung cancer by targeting multiple components of the Ras/rho GTPase molecular switch. Cancer Research, 67(21), 10379–10388. https://doi.org/10.1158/0008-5472.CAN-07-0677
Jiang,, M., Zhang,, E., Liang,, Z., Zhao,, Y., Zhang,, S., Xu,, H., … Zhen,, Y. (2019). Liposome‐based co‐delivery of 7‐O‐geranyl‐quercetin and IGF‐1R siRNA for the synergistic treatment of non‐small cell lung cancer. Journal of Drug Delivery Science and Technology, 54, 101316. https://doi.org/10.1016/j.jddst.2019.101316
Jimbo,, T., Hatanaka,, M., Komatsu,, T., Taira,, T., Kumazawa,, K., Maeda,, N., … Fujiwara,, K. (2019). DS‐1205b, a novel selective inhibitor of AXL kinase, blocks resistance to EGFR‐tyrosine kinase inhibitors in a non‐small cell lung cancer xenograft model. Oncotarget, 10(50), 5152–5167. https://doi.org/10.18632/oncotarget.27114
Kamba,, T., & McDonald,, D. M. (2007). Mechanisms of adverse effects of anti‐VEGF therapy for cancer. British Journal of Cancer, 96(12), 1788–1795. https://doi.org/10.1038/sj.bjc.6603813
Kamrani Moghaddam,, L., Ramezani Paschepari,, S., Zaimy,, M. A., Abdalaian,, A., & Jebali,, A. (2016). The inhibition of epidermal growth factor receptor signaling by hexagonal selenium nanoparticles modified by SiRNA. Cancer Gene Therapy, 23(9), 321–325. https://doi.org/10.1038/cgt.2016.38
Kato,, T., Daigo,, Y., Aragaki,, M., Ishikawa,, K., Sato,, M., Kondo,, S., & Kaji,, M. (2011). Overexpression of MAD2 predicts clinical outcome in primary lung cancer patients. Lung Cancer, 74(1), 124–131. https://doi.org/10.1016/j.lungcan.2011.01.025
Kauffmann‐Guerrero,, D., Syunyaeva,, Z., Kahnert,, K., & Tufman,, A. (2019). Excellent platinum dependent response to chemotherapy after relapse under TKI treatment in NSCLC with sensitizing EGFR mutations and no detectable resistance mutations: Three case studies. AME Case Reports, 3, 36. https://doi.org/10.21037/acr.2019.09.02
Ke,, B., Wei,, T., Huang,, Y., Gong,, Y., Wu,, G., Liu,, J., … Shi,, L. (2019). Interleukin‐7 resensitizes non‐small‐cell lung cancer to cisplatin via inhibition of ABCG2. Mediators of Inflammation, 2019, 7241418–7241417. https://doi.org/10.1155/2019/7241418
Kim,, D., Bach,, D., Fan,, Y., Luu,, T., Hong,, J., Park,, H., & Lee,, S. (2019). AXL degradation in combination with EGFR‐TKI can delay and overcome acquired resistance in human non‐small cell lung cancer cells. Cell Death %26 Disease, 10(5), 361. https://doi.org/10.1038/s41419-019-1601-6
Kim,, M. S., Park,, T. I., Lee,, Y. M., Jo,, Y. M., & Kim,, S. (2013). Expression of Id‐1 and VEGF in non‐small cell lung cancer. International Journal of Clinical and Experimental Pathology, 6(10), 2102–2111.
Kim,, Y. D., Park,, T. E., Singh,, B., Maharjan,, S., Choi,, Y. J., Choung,, P. H., … Cho,, C. S. (2015). Nanoparticle‐mediated delivery of siRNA for effective lung cancer therapy. Nanomedicine (London, England), 10(7), 1165–1188. https://doi.org/10.2217/nnm.14.214
Kris,, M. G., Gaspar,, L. E., Chaft,, J. E., Kennedy,, E. B., Azzoli,, C. G., Ellis,, P. M., … Weyant,, M. (2017). Adjuvant systemic therapy and adjuvant radiation therapy for stage I to IIIA completely resected non‐small‐cell lung cancers: American Society of Clinical Oncology/Cancer Care Ontario clinical practice guideline update. Journal of Clinical Oncology, 35(25), 2960–2974. https://doi.org/10.1200/JCO.2017.72.4401
Lee,, S. M. (2006). Is EGFR expression important in non‐small cell lung cancer? Thorax, 61(2), 98–99. https://doi.org/10.1136/thx.2005.047936
Lei,, L., Wang,, W. X., Yu,, Z. Y., Liang,, X. B., Pan,, W. W., Chen,, H. F., … Fang,, M. Y. (2020). A real‐world study in advanced non‐small cell lung cancer with KRAS mutations. Translational Oncology, 13(2), 329–335. https://doi.org/10.1016/j.tranon.2019.12.004
Li,, D., Hu,, C., & Li,, H. (2018). Survivin as a novel target protein for reducing the proliferation of cancer cells. Biomedical Reports, 8(5), 399–406. https://doi.org/10.3892/br.2018.1077
Li,, F., Wang,, Y., Chen,, W. L., Wang,, D. D., Zhou,, Y. J., You,, B. G., … Zhang,, X. N. (2019). Co‐delivery of VEGF siRNA and Etoposide for enhanced anti‐angiogenesis and anti‐proliferation effect via multi‐functional nanoparticles for Orthotopic non‐small cell lung cancer treatment. Theranostics, 9(20), 5886–5898. https://doi.org/10.7150/thno.32416
Liu,, T. C., Jin,, X., Wang,, Y., & Wang,, K. (2017). Role of epidermal growth factor receptor in lung cancer and targeted therapies. American Journal of Cancer Research, 7(2), 187–202.
Liu,, Y., Xie,, S., Zeng,, J., Song,, X., Tan,, M., He,, D., … Wang,, C. (2019). Adenylyl cyclaseassociated protein 1targeted nanoparticles as a novel strategy for the treatment of metastatic nonsmall cell lung cancer. International Journal of Oncology, 55(2), 462–472. https://doi.org/10.3892/ijo.2019.4822
Lv,, T., Li,, Z., Xu,, L., Zhang,, Y., Chen,, H., & Gao,, Y. (2018). Chloroquine in combination with aptamer‐modified nanocomplexes for tumor vessel normalization and efficient erlotinib/Survivin shRNA co‐delivery to overcome drug resistance in EGFR‐mutated non‐small cell lung cancer. Acta Biomaterialia, 76, 257–274. https://doi.org/10.1016/j.actbio.2018.06.034
Mahmoodi Chalbatani,, G., Dana,, H., Gharagouzloo,, E., Grijalvo,, S., Eritja,, R., Logsdon,, C. D., … Marmari,, V. (2019). Small interfering RNAs (siRNAs) in cancer therapy: A nano‐based approach. International Journal of Nanomedicine, 14, 3111–3128. https://doi.org/10.2147/IJN.S200253
Manchado,, E., Guillamot,, M., & Malumbres,, M. (2012). Killing cells by targeting mitosis. Cell Death and Differentiation, 19(3), 369–377. https://doi.org/10.1038/cdd.2011.197
Mansoori,, B., Mohammadi,, A., Davudian,, S., Shirjang,, S., & Baradaran,, B. (2017). The different mechanisms of cancer drug resistance: A brief review. Advanced Pharmaceutical Bulletin, 7(3), 339–348. https://doi.org/10.15171/apb.2017.041
Manzo,, A., Montanino,, A., Carillio,, G., Costanzo,, R., Sandomenico,, C., Normanno,, N., … Morabito,, A. (2017). Angiogenesis inhibitors in NSCLC. International Journal of Molecular Sciences, 18(10), 2021‐2038. https://doi.org/10.3390/ijms18102021
Mao,, C. Q., Xiong,, M. H., Liu,, Y., Shen,, S., Du,, X. J., Yang,, X. Z., … Wang,, J. (2014). Synthetic lethal therapy for KRAS mutant non‐small‐cell lung carcinoma with nanoparticle‐mediated CDK4 siRNA delivery. Molecular Therapy, 22(5), 964–973. https://doi.org/10.1038/mt.2014.18
Mattheolabakis,, G., Ling,, D., Ahmad,, G., & Amiji,, M. (2016). Enhanced anti‐tumor efficacy of lipid‐modified platinum derivatives in combination with Survivin silencing siRNA in resistant non‐small cell lung cancer. Pharmaceutical Research, 33(12), 2943–2953. https://doi.org/10.1007/s11095-016-2016-z
McCarroll,, J. A., Dwarte,, T., Baigude,, H., Dang,, J., Yang,, L., Erlich,, R. B., … Kavallaris,, M. (2015). Therapeutic targeting of polo‐like kinase 1 using RNA‐interfering nanoparticles (iNOPs) for the treatment of non‐small cell lung cancer. Oncotarget, 6(14), 12020–12034. https://doi.org/10.18632/oncotarget.2664
Meadows,, K. L., & Hurwitz,, H. I. (2012). Anti‐VEGF therapies in the clinic. Cold Spring Harbor Perspectives in Medicine, 2(10), 1–27. https://doi.org/10.1101/cshperspect.a006577
Michel,, L., Diaz‐Rodriguez,, E., Narayan,, G., Hernando,, E., Murty,, V. V., & Benezra,, R. (2004). Complete loss of the tumor suppressor MAD2 causes premature cyclin B degradation and mitotic failure in human somatic cells. Proceedings of the National Academy of Sciences of the United States of America, 101(13), 4459–4464. https://doi.org/10.1073/pnas.0306069101
Michel,, L. S., Liberal,, V., Chatterjee,, A., Kirchwegger,, R., Pasche,, B., Gerald,, W., … Benezra,, R. (2001). MAD2 haplo‐insufficiency causes premature anaphase and chromosome instability in mammalian cells. Nature, 409(6818), 355–359. https://doi.org/10.1038/35053094
Mogi,, A., & Kuwano,, H. (2011). TP53 mutations in nonsmall cell lung cancer. Journal of Biomedicine %26 Biotechnology, 2011, 583929. https://doi.org/10.1155/2011/583929
Molina,, J. R., Yang,, P., Cassivi,, S. D., Schild,, S. E., & Adjei,, A. A. (2008). Non‐small cell lung cancer: Epidemiology, risk factors, treatment, and survivorship. Mayo Clinic Proceedings, 83(5), 584–594. https://doi.org/10.4065/83.5.584
Morales,, D. R., & Morris,, A. D. (2015). Metformin in cancer treatment and prevention. Annual Review of Medicine, 66, 17–29. https://doi.org/10.1146/annurev-med-062613-093128
Nascimento,, A. V., Gattacceca,, F., Singh,, A., Bousbaa,, H., Ferreira,, D., Sarmento,, B., & Amiji,, M. M. (2016). Biodistribution and pharmacokinetics of Mad2 siRNA‐loaded EGFR‐targeted chitosan nanoparticles in cisplatin sensitive and resistant lung cancer models. Nanomedicine (London, England), 11(7), 767–781. https://doi.org/10.2217/nnm.16.14
Nascimento,, A. V., Singh,, A., Bousbaa,, H., Ferreira,, D., Sarmento,, B., & Amiji,, M. M. (2014). Mad2 checkpoint gene silencing using epidermal growth factor receptor‐targeted chitosan nanoparticles in non‐small cell lung cancer model. Molecular Pharmaceutics, 11(10), 3515–3527. https://doi.org/10.1021/mp5002894
Nascimento,, A. V., Singh,, A., Bousbaa,, H., Ferreira,, D., Sarmento,, B., & Amiji,, M. M. (2017). Overcoming cisplatin resistance in non‐small cell lung cancer with Mad2 silencing siRNA delivered systemically using EGFR‐targeted chitosan nanoparticles. Acta Biomaterialia, 47, 71–80. https://doi.org/10.1016/j.actbio.2016.09.045
Niklinska,, W., Burzykowski,, T., Chyczewski,, L., & Niklinski,, J. (2001). Expression of vascular endothelial growth factor (VEGF) in non‐small cell lung cancer (NSCLC): Association with p53 gene mutation and prognosis. Lung Cancer, 34(Suppl 2), S59–S64. https://doi.org/10.1016/s0169-5002(01)00346-4
Okura,, N., Nishioka,, N., Yamada,, T., Taniguchi,, H., Tanimura,, K., Katayama,, Y., … Takayama,, K. (2020). ONO‐7475, a novel AXL inhibitor, suppresses the adaptive resistance to initial EGFR‐TKI treatment in EGFR‐mutated non‐small cell lung cancer. Clinical Cancer Research, 26(9), 2244–2256. https://doi.org/10.1158/1078-0432.CCR-19-2321
Pai,, S. I., Lin,, Y. Y., Macaes,, B., Meneshian,, A., Hung,, C. F., & Wu,, T. C. (2006). Prospects of RNA interference therapy for cancer. Gene Therapy, 13(6), 464–477. https://doi.org/10.1038/sj.gt.3302694
Pecot,, C. V., Wu,, S. Y., Bellister,, S., Filant,, J., Rupaimoole,, R., Hisamatsu,, T., … Sood,, A. K. (2014). Therapeutic silencing of KRAS using systemically delivered siRNAs. Molecular Cancer Therapeutics, 13(12), 2876–2885. https://doi.org/10.1158/1535-7163.MCT-14-0074
Perepelyuk,, M., Shoyele,, O., Birbe,, R., Thangavel,, C., Liu,, Y., Den,, R. B., … Shoyele,, S. A. (2017). siRNA‐encapsulated hybrid nanoparticles target mutant K‐ras and inhibit metastatic tumor burden in a mouse model of lung cancer. Molecular Therapy ‐ Nucleic Acids, 6, 259–268. https://doi.org/10.1016/j.omtn.2016.12.009
Pernicova,, I., & Korbonits,, M. (2014). Metformin—Mode of action and clinical implications for diabetes and cancer. Nature Reviews. Endocrinology, 10(3), 143–156. https://doi.org/10.1038/nrendo.2013.256
Prabhakar,, C. N. (2015). Epidermal growth factor receptor in non‐small cell lung cancer. Translational Lung Cancer Research, 4(2), 110–118. https://doi.org/10.3978/j.issn.2218-6751.2015.01.01
Prokop,, A., & Davidson,, J. M. (2008). Nanovehicular intracellular delivery systems. Journal of Pharmaceutical Sciences, 97(9), 3518–3590. https://doi.org/10.1002/jps.21270
Reda,, M., Ngamcherdtrakul,, W., Gu,, S., Bejan,, D. S., Siriwon,, N., Gray,, J. W., & Yantasee,, W. (2019). PLK1 and EGFR targeted nanoparticle as a radiation sensitizer for non‐small cell lung cancer. Cancer Letters, 467, 9–18. https://doi.org/10.1016/j.canlet.2019.09.014
Resnier,, P., Montier,, T., Mathieu,, V., Benoit,, J. P., & Passirani,, C. (2013). A review of the current status of siRNA nanomedicines in the treatment of cancer. Biomaterials, 34(27), 6429–6443. https://doi.org/10.1016/j.biomaterials.2013.04.060
Rizvi,, S. A. A., & Saleh,, A. M. (2018). Applications of nanoparticle systems in drug delivery technology. Saudi Pharmaceutical Journal, 26(1), 64–70. https://doi.org/10.1016/j.jsps.2017.10.012
Rossi,, A., & Di Maio,, M. (2016). Platinum‐based chemotherapy in advanced non‐small‐cell lung cancer: Optimal number of treatment cycles. Expert Review of Anticancer Therapy, 16(6), 653–660. https://doi.org/10.1586/14737140.2016.1170596
Santoni‐Rugiu,, E., Melchior,, L. C., Urbanska,, E. M., Jakobsen,, J. N., Stricker,, K., Grauslund,, M., & Sorensen,, J. B. (2019). Intrinsic resistance to EGFR‐tyrosine kinase inhibitors in EGFR‐mutant non‐small cell lung cancer: Differences and similarities with acquired resistance. Cancers (Basel), 11(7), 923–980. https://doi.org/10.3390/cancers11070923
Setten,, R. L., Rossi,, J. J., & Han,, S. P. (2019). The current state and future directions of RNAi‐based therapeutics. Nature Reviews. Drug Discovery, 18(6), 421–446. https://doi.org/10.1038/s41573-019-0017-4
Shen,, S., Mao,, C. Q., Yang,, X. Z., Du,, X. J., Liu,, Y., Zhu,, Y. H., & Wang,, J. (2014). Cationic lipid‐assisted polymeric nanoparticle mediated GATA2 siRNA delivery for synthetic lethal therapy of KRAS mutant non‐small‐cell lung carcinoma. Molecular Pharmaceutics, 11(8), 2612–2622. https://doi.org/10.1021/mp400714z
Shi,, K., Zhao,, Y., Miao,, L., Satterlee,, A., Haynes,, M., Luo,, C., … Huang,, L. (2017). Dual functional LipoMET mediates envelope‐type nanoparticles to combinational oncogene silencing and tumor growth inhibition. Molecular Therapy, 25(7), 1567–1579. https://doi.org/10.1016/j.ymthe.2017.02.008
Sonoda,, T., Nishikawa,, S., Sakakibara,, R., Saiki,, M., Ariyasu,, R., Koyama,, J., … Nishio,, M. (2018). EGFR T790M mutation after chemotherapy for small cell lung cancer transformation of EGFR‐positive non‐small cell lung cancer. Respiratory Medicine Case Reports, 24, 19–21. https://doi.org/10.1016/j.rmcr.2018.03.009
Sotillo,, R., Hernando,, E., Diaz‐Rodriguez,, E., Teruya‐Feldstein,, J., Cordon‐Cardo,, C., Lowe,, S. W., & Benezra,, R. (2007). Mad2 overexpression promotes aneuploidy and tumorigenesis in mice. Cancer Cell, 11(1), 9–23. https://doi.org/10.1016/j.ccr.2006.10.019
Srikar,, R., Suresh,, D., Zambre,, A., Taylor,, K., Chapman,, S., Leevy,, M., … Kannan,, R. (2016). Targeted nanoconjugate co‐delivering siRNA and tyrosine kinase inhibitor to KRAS mutant NSCLC dissociates GAB1‐SHP2 post oncogene knockdown. Scientific Reports, 6, 30245. https://doi.org/10.1038/srep30245
Sunaga,, N., Shames,, D. S., Girard,, L., Peyton,, M., Larsen,, J. E., Imai,, H., … Minna,, J. D. (2011). Knockdown of oncogenic KRAS in non‐small cell lung cancers suppresses tumor growth and sensitizes tumor cells to targeted therapy. Molecular Cancer Therapeutics, 10(2), 336–346. https://doi.org/10.1158/1535-7163.MCT-10-0750
Suresh,, D., Zambre,, A., Mukherjee,, S., Ghoshdastidar,, S., Jiang,, Y., Joshi,, T., … Kannan,, R. (2019). Silencing AXL by covalent siRNA‐gelatin‐antibody nanoconjugate inactivates mTOR/EMT pathway and stimulates p53 for TKI sensitization in NSCLC. Nanomedicine, 20, 102007. https://doi.org/10.1016/j.nano.2019.04.010
Takamochi,, K., Oh,, S., Matsunaga,, T., & Suzuki,, K. (2017). Prognostic impacts of EGFR mutation status and subtype in patients with surgically resected lung adenocarcinoma. The Journal of Thoracic and Cardiovascular Surgery, 154(5), 1768–1774 e1761. https://doi.org/10.1016/j.jtcvs.2017.06.062
Tao,, S., Wang,, S., Moghaddam,, S. J., Ooi,, A., Chapman,, E., Wong,, P. K., & Zhang,, D. D. (2014). Oncogenic KRAS confers chemoresistance by upregulating NRF2. Cancer Research, 74(24), 7430–7441. https://doi.org/10.1158/0008-5472.CAN-14-1439
Taratula,, O., Garbuzenko,, O. B., Chen,, A. M., & Minko,, T. (2011). Innovative strategy for treatment of lung cancer: Targeted nanotechnology‐based inhalation co‐delivery of anticancer drugs and siRNA. Journal of Drug Targeting, 19(10), 900–914. https://doi.org/10.3109/1061186X.2011.622404
Taratula,, O., Kuzmov,, A., Shah,, M., Garbuzenko,, O. B., & Minko,, T. (2013). Nanostructured lipid carriers as multifunctional nanomedicine platform for pulmonary co‐delivery of anticancer drugs and siRNA. Journal of Controlled Release, 171(3), 349–357. https://doi.org/10.1016/j.jconrel.2013.04.018
Tatiparti,, K., Sau,, S., Kashaw,, S. K., & Iyer,, A. K. (2017). siRNA delivery strategies: A comprehensive review of recent developments. Nanomaterials (Basel), 7(4), 77–94. https://doi.org/10.3390/nano7040077
Thomas,, A., Rajan,, A., & Giaccone,, G. (2012). Tyrosine kinase inhibitors in lung cancer. Hematology/Oncology Clinics of North America, 26(3), 589–605, viii. https://doi.org/10.1016/j.hoc.2012.02.001
Tseng,, J. S., Yang,, T. Y., Tsai,, C. R., Chen,, K. C., Hsu,, K. H., Tsai,, M. H., … Chang,, G. C. (2015). Dynamic plasma EGFR mutation status as a predictor of EGFR‐TKI efficacy in patients with EGFR‐mutant lung adenocarcinoma. Journal of Thoracic Oncology, 10(4), 603–610. https://doi.org/10.1097/JTO.0000000000000443
Umelo,, I. A., Wever,, O. D., Kronenberger,, P., Noor,, A., Teugels,, E., Chen,, G., … Greve,, J. D. (2015). Combined inhibition of rho‐associated protein kinase and EGFR suppresses the invasive phenotype in EGFR‐dependent lung cancer cells. Lung Cancer, 90(2), 167–174. https://doi.org/10.1016/j.lungcan.2015.08.008
Varshosaz,, J., & Taymouri,, S. (2015). Hollow inorganic nanoparticles as efficient carriers for siRNA delivery: A comprehensive review. Current Pharmaceutical Design, 21(29), 4310–4328. https://doi.org/10.2174/1381612821666150901103937
Vasan,, N., Baselga,, J., & Hyman,, D. M. (2019). A view on drug resistance in cancer. Nature, 575(7782), 299–309. https://doi.org/10.1038/s41586-019-1730-1
Wang,, M., Wang,, J., Li,, B., Meng,, L., & Tian,, Z. (2017). Recent advances in mechanism‐based chemotherapy drug‐siRNA pairs in co‐delivery systems for cancer: A review. Colloids and Surfaces. B, Biointerfaces, 157, 297–308. https://doi.org/10.1016/j.colsurfb.2017.06.002
Wesarg,, E., Hoffarth,, S., Wiewrodt,, R., Kroll,, M., Biesterfeld,, S., Huber,, C., & Schuler,, M. (2007). Targeting BCL‐2 family proteins to overcome drug resistance in non‐small cell lung cancer. International Journal of Cancer, 121(11), 2387–2394. https://doi.org/10.1002/ijc.22977
Xue,, W., Dahlman,, J. E., Tammela,, T., Khan,, O. F., Sood,, S., Dave,, A., … Jacks,, T. (2014). Small RNA combination therapy for lung cancer. Proceedings of the National Academy of Sciences of the United States of America, 111(34), E3553–E3561. https://doi.org/10.1073/pnas.1412686111
Yamamoto,, H., Shigematsu,, H., Nomura,, M., Lockwood,, W. W., Sato,, M., Okumura,, N., … Gazdar,, A. F. (2008). PIK3CA mutations and copy number gains in human lung cancers. Cancer Research, 68(17), 6913–6921. https://doi.org/10.1158/0008-5472.CAN-07-5084
Yang,, H., Fu,, J. H., Hu,, Y., Huang,, W. Z., Zheng,, B., Wang,, G., … Wen,, J. (2008). Influence of SiRNA targeting survivin on chemosensitivity of H460/cDDP lung cancer cells. The Journal of International Medical Research, 36(4), 734–747. https://doi.org/10.1177/147323000803600416
Yang,, H., Liang,, S. Q., Schmid,, R. A., & Peng,, R. W. (2019). New horizons in KRAS‐mutant lung cancer: Dawn after darkness. Frontiers in Oncology, 9, 953. https://doi.org/10.3389/fonc.2019.00953
Yang,, Y., Bai,, Y., Xie,, G., Zhang,, N., Ma,, Y. P., Chen,, L. J., … Deng,, H. X. (2010). Efficient inhibition of non‐small‐cell lung cancer xenograft by systemic delivery of plasmid‐encoding short‐hairpin RNA targeting VEGF. Cancer Biotherapy %26 Radiopharmaceuticals, 25(1), 65–73. https://doi.org/10.1089/cbr.2009.0692
Yang,, Y., Hu,, Y., Wang,, Y., Li,, J., Liu,, F., & Huang,, L. (2012). Nanoparticle delivery of pooled siRNA for effective treatment of non‐small cell lung cancer. Molecular Pharmaceutics, 9(8), 2280–2289. https://doi.org/10.1021/mp300152v
Yoh,, K., Hosomi,, Y., Kasahara,, K., Yamada,, K., Takahashi,, T., Yamamoto,, N., … Nakagawa,, K. (2016). A randomized, double‐blind, phase II study of ramucirumab plus docetaxel vs placebo plus docetaxel in Japanese patients with stage IV non‐small cell lung cancer after disease progression on platinum‐based therapy. Lung Cancer, 99, 186–193. https://doi.org/10.1016/j.lungcan.2016.07.019
Yonesaka,, K., Tamura,, K., Kurata,, T., Satoh,, T., Ikeda,, M., Fukuoka,, M., & Nakagawa,, K. (2006). Small interfering RNA targeting survivin sensitizes lung cancer cell with mutant p53 to adriamycin. International Journal of Cancer, 118(4), 812–820. https://doi.org/10.1002/ijc.21350
Yu,, H., Zou,, Y., Jiang,, L., Yin,, Q., He,, X., Chen,, L., … Li,, Y. (2013). Induction of apoptosis in non‐small cell lung cancer by downregulation of MDM2 using pH‐responsive PMPC‐b‐PDPA/siRNA complex nanoparticles. Biomaterials, 34(11), 2738–2747. https://doi.org/10.1016/j.biomaterials.2012.12.042
Yu,, L., Liu,, S., Guo,, W., Zhang,, B., Liang,, Y., & Feng,, Q. (2012). Upregulation of Mad2 facilitates in vivo and in vitro osteosarcoma progression. Oncology Reports, 28(6), 2170–2176. https://doi.org/10.3892/or.2012.2032
Yuan,, A., Yu,, C. J., Luh,, K. T., Chen,, W. J., Lin,, F. Y., Kuo,, S. H., & Yang,, P. C. (2000). Quantification of VEGF mRNA expression in non‐small cell lung cancer using a real‐time quantitative reverse transcription‐PCR assay and a comparison with quantitative competitive reverse transcription‐PCR. Laboratory Investigation, 80(11), 1671–1680. https://doi.org/10.1038/labinvest.3780177
Yuan,, Z. Q., Chen,, W. L., You,, B. G., Liu,, Y., Yang,, S. D., Li,, J. Z., … Zhang,, X. N. (2017). Multifunctional nanoparticles co‐delivering EZH2 siRNA and etoposide for synergistic therapy of orthotopic non‐small‐cell lung tumor. Journal of Controlled Release, 268, 198–211. https://doi.org/10.1016/j.jconrel.2017.10.025
Zappa,, C., & Mousa,, S. A. (2016). Non‐small cell lung cancer: Current treatment and future advances. Translational Lung Cancer Research, 5(3), 288–300. https://doi.org/10.21037/tlcr.2016.06.07
Zhang,, G., Wang,, M., Zhao,, H., & Cui,, W. (2018). Function of Axl receptor tyrosine kinase in non‐small cell lung cancer. Oncology Letters, 15(3), 2726–2734. https://doi.org/10.3892/ol.2017.7694
Zhang,, J. W., Zhao,, Y. Y., Guo,, Y., Xue,, C., Hu,, Z. H., Huang,, Y., … Zhang,, L. (2014). The impact of both platinum‐based chemotherapy and EGFR‐TKIs on overall survival of patients with advanced non‐small cell lung cancer. Chinese Journal of Cancer, 33(2), 105–114. https://doi.org/10.5732/cjc.012.10274
Zhang,, W., Xu,, W., Lan,, Y., He,, X., Liu,, K., & Liang,, Y. (2019). Antitumor effect of hyaluronic‐acid‐modified chitosan nanoparticles loaded with siRNA for targeted therapy for non‐small cell lung cancer. International Journal of Nanomedicine, 14, 5287–5301. https://doi.org/10.2147/IJN.S203113
Zhang,, Y., Peng,, L., Mumper,, R. J., & Huang,, L. (2013). Combinational delivery of c‐myc siRNA and nucleoside analogs in a single, synthetic nanocarrier for targeted cancer therapy. Biomaterials, 34(33), 8459–8468. https://doi.org/10.1016/j.biomaterials.2013.07.050
Zhang,, Y., Schwerbrock,, N. M., Rogers,, A. B., Kim,, W. Y., & Huang,, L. (2013). Codelivery of VEGF siRNA and gemcitabine monophosphate in a single nanoparticle formulation for effective treatment of NSCLC. Molecular Therapy, 21(8), 1559–1569. https://doi.org/10.1038/mt.2013.120
Zhu,, X., Xu,, Y., Solis,, L. M., Tao,, W., Wang,, L., Behrens,, C., … Shi,, J. (2015). Long‐circulating siRNA nanoparticles for validating Prohibitin1‐targeted non‐small cell lung cancer treatment. Proceedings of the National Academy of Sciences of the United States of America, 112(25), 7779–7784. https://doi.org/10.1073/pnas.1505629112
Zirlik,, K., & Duyster,, J. (2018). Anti‐Angiogenics: Current situation and future perspectives. Oncology Research and Treatment, 41(4), 166–171. https://doi.org/10.1159/000488087
Zou,, M., Xia,, S., Zhuang,, L., Han,, N., Chu,, Q., Chao,, T., … Yu,, S. (2013). Knockdown of the Bcl‐2 gene increases sensitivity to EGFR tyrosine kinase inhibitors in the H1975 lung cancer cell line harboring T790M mutation. International Journal of Oncology, 42(6), 2094–2102. https://doi.org/10.3892/ijo.2013.1895

Further Reading

Peng,, Y., Yang,, J., Zhang,, E., Sun,, H., Wang,, Q., Wang,, T., … Shi,, C. (2012). Human positive coactivator 4 is a potential novel therapeutic target in non‐small cell lung cancer. Cancer Gene Therapy, 19(10), 690–696. https://doi.org/10.1038/cgt.2012.52
Wang,, S., Pan,, H., Liu,, D., Mao,, N., Zuo,, C., Li,, L., … Wu,, J. (2015). Excision repair cross complementation group 1 is a chemotherapy‐tolerating gene in cisplatin‐based treatment for non‐small cell lung cancer. International Journal of Oncology, 46(2), 809–817. https://doi.org/10.3892/ijo.2014.2784

Access to this WIREs title is by subscription only.

Recommend to Your
Librarian Now!

The latest WIREs articles in your inbox

Sign Up for Article Alerts