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Recent Patents on Anti-Cancer Drug Discovery

Editor-in-Chief

ISSN (Print): 1574-8928
ISSN (Online): 2212-3970

Review Article

Gefitinib: An Updated Review of its Role in the Cancer Management, its Nanotechnological Interventions, Recent Patents and Clinical Trials

Author(s): Pankaj Kumar, Bharti Mangla*, Shamama Javed, Waquar Ahsan, Pankaj Musyuni, Aarif Ahsan and Geeta Aggarwal*

Volume 18, Issue 4, 2023

Published on: 03 November, 2022

Page: [448 - 469] Pages: 22

DOI: 10.2174/1574892818666221026164940

Price: $65

Abstract

Background: Gefitinib, a tyrosine kinase inhibitor, is effectively used in the targeted treatment of malignant conditions. It suppresses the signal transduction cascades leading to cell proliferation in the tumors and is now currently approved in several countries globally as secondline and third-line treatment for non-small cell lung cancer (NSCLC).

Objective: This review is aimed to summarize the journey of gefitinib as an established anticancer drug for the management of various cancers. Moreover, this review will focus on the mechanism of action, established anticancer activities, combination therapy, nanoformulations, as well as recent clinical trials and patents on gefitinib.

Methods: The data for this review was collected from scientific databases such as PubMed, Science Direct, Google Scholar, etc. Recent patents on gefitinib granted in the last two years were collected from databases Patentscope, USPTO, Espacenet, InPASS and Google Patents. Data for the recent clinical trials were obtained from the U.S. National Library of Medicine database.

Results: Recent pre-clinical and clinical studies during the period 2015-2021 demonstrating the efficacy of gefitinib were selected and summarized. Total 31 patents were granted in the year 2020-2021 concerning gefitinib. The efficacy of gefitinib against lung cancer, as well as other cancer types, including breast, prostate, colon, cervix etc., was reviewed.

Conclusion: Gefitinib showed significant advantages in being more effective, safer and more stable, and the associated biopharmaceutical problems are addressed by the application of nanotechnology. The combination therapy using gefitinib and various anticancer molecules of natural and synthetic origin has shown an improved anticancer profile.

Keywords: Gefitinib, cancer, nanotechnology, patents, clinical trials, NSCLC.

[1]
Shah NT, Kris MG, Pao W, et al. Practical management of patients with non-small-cell lung cancer treated with gefitinib. J Clin Oncol 2005; 23(1): 165-74.
[http://dx.doi.org/10.1200/JCO.2005.04.057] [PMID: 15557594]
[2]
Sever R, Brugge JS. Signal transduction in cancer. Cold Spring Harb Perspect Med 2015; 5(4): a006098.
[http://dx.doi.org/10.1101/cshperspect.a006098] [PMID: 25833940]
[3]
Maennling AE, Tur MK, Niebert M, et al. Molecular targeting therapy against EGFR family in breast cancer: progress and future potentials. Cancers 2019; 11(12): 1826.
[http://dx.doi.org/10.3390/cancers11121826] [PMID: 31756933]
[4]
Vansteenkiste JF. Gefitinib (Iressa®): a novel treatment for non-small cell lung cancer. Expert Rev Anticancer Ther 2004; 4(1): 5-17.
[http://dx.doi.org/10.1586/14737140.4.1.5] [PMID: 14748652]
[5]
Lynch TJ, Bell DW, Sordella R, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 2004; 350(21): 2129-39.
[http://dx.doi.org/10.1056/NEJMoa040938] [PMID: 15118073]
[6]
Yarden Y, Sliwkowski MX. Untangling the ErbB signalling network. Nat Rev Mol Cell Biol 2001; 2(2): 127-37.
[http://dx.doi.org/10.1038/35052073] [PMID: 11252954]
[7]
Citri A, Yarden Y. EGF–ERBB signalling: towards the systems level. Nat Rev Mol Cell Biol 2006; 7(7): 505-16.
[http://dx.doi.org/10.1038/nrm1962] [PMID: 16829981]
[8]
Yamaoka T, Ohba M, Ohmori T. Molecular-targeted therapies for epidermal growth factor receptor and its resistance mechanisms. Int J Mol Sci 2017; 18(11): 2420.
[http://dx.doi.org/10.3390/ijms18112420] [PMID: 29140271]
[9]
Greenhalgh J, Bagust A, Boland A, et al. Erlotinib & gefitinib for treating non-small cell lung cancer that has progressed following prior chemotherapy: a systematic review and economic evaluation. Health Technol Assess 2015; 19(47): 1-8.
[http://dx.doi.org/10.3310/hta19470] [PMID: 26134145]
[10]
Karachaliou N, Fernandez-Bruno M, 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]
[11]
Douillard J-Y, Ostoros G, Cobo M, et al. First-line gefitinib in Caucasian EGFR mutation-positive NSCLC patients: a phase-IV, open-label, single-arm study. Br J Cancer 2014; 110(1): 55-62.
[http://dx.doi.org/10.1038/bjc.2013.721] [PMID: 24263064]
[12]
Kazandjian D, Blumenthal GM, Yuan W, He K, Keegan P, Pazdur R. FDA approval of gefitinib for the treatment of patients with metastatic EGFR mutation-positive non-small cell lung cancer. Clin Cancer Res 2016; 22(6): 1307-12.
[http://dx.doi.org/10.1158/1078-0432.CCR-15-2266] [PMID: 26980062]
[13]
Rawluk J, Waller CF. Gefitinib. Small Molecules in Oncology 2018; pp. 235-46.
[14]
Giaccone G. The role of gefitinib in lung cancer treatment. Clin Cancer Res 2004; 10(12): S4233-7.
[http://dx.doi.org/10.1158/1078-0432.CCR-040005] [PMID: 15217964]
[15]
Rahman AFMM, Korashy HM, Kassem MG. Gefitinib. Profiles Drug Subst Excip Relat Methodol 2014; 39: 239-64.
[http://dx.doi.org/10.1016/B978-0-12-800173-8.00005-2] [PMID: 24794908]
[16]
Fahad Ullah M. Breast cancer: current perspectives on the disease status. Adv Exp Med Biol 2019; 1152: 51-64.
[http://dx.doi.org/10.1007/978-3-030-20301-6_4] [PMID: 31456179]
[17]
Ataollahi MR, Sharifi J, Paknahad MR, Paknahad A. Breast cancer and associated factors: a review. J Med Life 2015; 8(Spec Iss 4): 6-11. PMID: 28316699
[18]
Nakai K, Hung MC, Yamaguchi H. A perspective on anti-EGFR therapies targeting triple-negative breast cancer. Am J Cancer Res 2016; 6(8): 1609-23.
[PMID: 27648353]
[19]
Yin L, Duan JJ, Bian XW, Yu S. Triple-negative breast cancer molecular subtyping and treatment progress. Breast Cancer Res 2020; 22(1): 61.
[http://dx.doi.org/10.1186/s13058-020-01296-5] [PMID: 32517735]
[20]
Segovia-Mendoza M, González-González ME, Barrera D, Díaz L, García-Becerra R. Efficacy and mechanism of action of the tyrosine kinase inhibitors gefitinib, lapatinib and neratinib in the treatment of HER2-positive breast cancer: preclinical and clinical evidence. Am J Cancer Res 2015; 5(9): 2531-61.
[PMID: 26609467]
[21]
Seshacharyulu P, Ponnusamy MP, Haridas D, Jain M, Ganti AK, Batra SK. Targeting the EGFR signaling pathway in cancer therapy. Expert Opin Ther Targets 2012; 16(1): 15-31.
[http://dx.doi.org/10.1517/14728222.2011.648617] [PMID: 22239438]
[22]
Mishra R, Patel H, Alanazi S, Yuan L, Garrett JT. HER3 signaling and targeted therapy in cancer. Oncol Rev 2018; 12(1): 355.
[http://dx.doi.org/10.4081/oncol.2018.355] [PMID: 30057690]
[23]
Veronesi U, Boyle P, Goldhirsch A, Orecchia R, Viale G. Breast cancer. Lancet 2005; 365(9472): 1727-41.
[http://dx.doi.org/10.1016/S0140-6736(05)66546-4] [PMID: 15894099]
[24]
Nayek S, Raghavendra NM, Sajeev Kumar B. Development of novel S PC-3 gefitinib lipid nanoparticles for effective drug delivery in breast cancer. Tissue distribution studies and cell cytotoxicity analysis. J Drug Deliv Sci Technol 2021; 61: 102073.
[http://dx.doi.org/10.1016/j.jddst.2020.102073]
[25]
Piechocki MP, Yoo GH, Dibbley SK, Lonardo F. Breast cancer expressing the activated HER2/neu is sensitive to gefitinib in vitro and in vivo and acquires resistance through a novel point mutation in the HER2/neu. Cancer Res 2007; 67(14): 6825-43.
[http://dx.doi.org/10.1158/0008-5472.CAN-07-0765] [PMID: 17638894]
[26]
Warburton C, Dragowska WH, Gelmon K, et al. Treatment of HER-2/neu overexpressing breast cancer xenograft models with trastuzumab (Herceptin) and gefitinib (ZD1839): drug combination effects on tumor growth, HER-2/neu and epidermal growth factor receptor expression, and viable hypoxic cell fraction. Clin Cancer Res 2004; 10(7): 2512-24.
[http://dx.doi.org/10.1158/1078-0432.CCR-03-0244] [PMID: 15073131]
[27]
Takabatake D, Fujita T, Shien T, et al. Tumor inhibitory effect of gefitinib (ZD1839, Iressa) and taxane combination therapy in EGFR-overexpressing breast cancer cell lines (MCF7/ADR, MDA-MB-231). Int J Cancer 2007; 120(1): 181-8.
[http://dx.doi.org/10.1002/ijc.22187] [PMID: 17036319]
[28]
Mehta A, Jose W, Pavithran K, Triavadi G. The role of Gefitinib in patients with non-small-cell lung cancer in India. Indian J Palliat Care 2013; 19(1): 48-53.
[http://dx.doi.org/10.4103/0973-1075.110237] [PMID: 23766595]
[29]
Yuan Y, Li XF, Chen JQ, Dong CX, Weng SS, Huang JJ. Critical appraisal of the role of gefitinib in the management of locally advanced or metastatic non-small cell lung cancer. OncoTargets Ther 2014; 7: 841-52.
[http://dx.doi.org/10.2147/OTT.S34124] [PMID: 24920926]
[30]
Gridelli C, Rossi A, Maione P. Treatment of non-small-cell lung cancer: state of the art and development of new biologic agents. Oncogene 2003; 22(42): 6629-38.
[http://dx.doi.org/10.1038/sj.onc.1206957] [PMID: 14528288]
[31]
Zhao ZQ, Yu ZY, Li J, Ouyang XN. Gefitinib induces lung cancer cell autophagy and apoptosis via blockade of the PI3K/AKT/mTOR pathway. Oncol Lett 2016; 12(1): 63-8.
[http://dx.doi.org/10.3892/ol.2016.4606] [PMID: 27347100]
[32]
Yamaguchi NH, Mayer IA, Malzyner A, et al. Gefitinib and celecoxib in advanced metastatic gastrointestinal tumors: a pilot feasibility study. J Gastrointest Oncol 2014; 5(1): 57-66.
[http://dx.doi.org/10.3978/j.issn.2078-6891.2013.056] [PMID: 24490043]
[33]
Ponz-Sarvisé M, Rodríguez J, Viudez A, et al. Epidermal growth factor receptor inhibitors in colorectal cancer treatment: What’s new? World J Gastroenterol 2007; 13(44): 5877-87.
[http://dx.doi.org/10.3748/wjg.v13.i44.5877] [PMID: 17990353]
[34]
Cascinu S, Berardi R, Salvagni S, et al. A combination of gefitinib and FOLFOX-4 as first-line treatment in advanced colorectal cancer patients. A GISCAD multicentre phase II study including a biological analysis of EGFR overexpression, amplification and NF-kB activation. Br J Cancer 2008; 98(1): 71-6.
[http://dx.doi.org/10.1038/sj.bjc.6604121] [PMID: 18059397]
[35]
Fisher GA, Kuo T, Ramsey M, et al. A phase II study of gefitinib, 5-fluorouracil, leucovorin, and oxaliplatin in previously untreated patients with metastatic colorectal cancer. Clin Cancer Res 2008; 14(21): 7074-9.
[http://dx.doi.org/10.1158/1078-0432.CCR-08-1014] [PMID: 18981005]
[36]
Pimple S, Mishra G, Shastri S. Global strategies for cervical cancer prevention. Curr Opin Obstet Gynecol 2016; 28(1): 4-10.
[http://dx.doi.org/10.1097/GCO.0000000000000241] [PMID: 26642063]
[37]
Yang Z, Hackshaw A, Feng Q, et al. Comparison of gefitinib, erlotinib and afatinib in non‐small cell lung cancer: A meta‐analysis. Int J Cancer 2017; 140(12): 2805-19.
[http://dx.doi.org/10.1002/ijc.30691] [PMID: 28295308]
[38]
Yang RF, Yu B, Zhang RQ, et al. Bevacizumab and gefitinib enhanced whole-brain radiation therapy for brain metastases due to non-small-cell lung cancer. Braz J Med Biol Res 2018; 51(1): e6073.
[http://dx.doi.org/10.1590/1414-431x20176073] [PMID: 29185589]
[39]
Goncalves A, Fabbro M, Lhommé C, et al. A phase II trial to evaluate gefitinib as second- or third-line treatment in patients with recurring locoregionally advanced or metastatic cervical cancer. Gynecol Oncol 2008; 108(1): 42-6.
[http://dx.doi.org/10.1016/j.ygyno.2007.07.057] [PMID: 17980406]
[40]
Zheng J, Yu J, Yang M, Tang L. Gefitinib suppresses cervical cancer progression by inhibiting cell cycle progression and epithelial mesenchymal transition. Exp Ther Med 2019; 18(3): 1823-30.
[http://dx.doi.org/10.3892/etm.2019.7754] [PMID: 31410143]
[41]
Sharma DN, Rath GK, Julka PK, Gandhi AK, Jagadesan P, Kumar S. Role of gefitinib in patients with recurrent or metastatic cervical carcinoma ineligible or refractory to systemic chemotherapy: first study from Asia. Int J Gynecol Cancer 2013; 23(4): 705-9.
[http://dx.doi.org/10.1097/IGC.0b013e31828b1699] [PMID: 23466569]
[42]
Merriel SWD, Funston G, Hamilton W. Prostate cancer in primary care. Adv Ther 2018; 35(9): 1285-94.
[http://dx.doi.org/10.1007/s12325-018-0766-1] [PMID: 30097885]
[43]
Bonaccorsi L, Marchiani S, Muratori M, Forti G, Baldi E. Gefitinib (‘IRESSA’, ZD1839) inhibits EGF-induced invasion in prostate cancer cells by suppressing PI3K/AKT activation. J Cancer Res Clin Oncol 2004; 130(10): 604-14.
[http://dx.doi.org/10.1007/s00432-004-0581-8] [PMID: 15258753]
[44]
Lin JZ, Hameed I, Xu Z, Yu Y, Ren ZY, Zhu JG. Efficacy of gefitinib celecoxib combination therapy in docetaxel resistant prostate cancer. Oncol Rep 2018; 40(4): 2242-50.
[http://dx.doi.org/10.3892/or.2018.6595] [PMID: 30066906]
[45]
Formento P, Hannoun-Levi JM, Gérard F, et al. Gefitinib–trastuzumab combination on hormone-refractory prostate cancer xenograft. Eur J Cancer 2005; 41(10): 1467-73.
[http://dx.doi.org/10.1016/j.ejca.2005.03.021] [PMID: 15919200]
[46]
M B, Br S, Dk S, et al. Potential of herbal drug & antibiotic combination therapy: a new approach to treat multidrug resistant bacteria. Pharm Anal Acta 2016; 7(11): 11. http://dx.doi.org/10.4172/2153-2435.1000523
[47]
Xin J, Wang J, Shen H, et al. Curcumin co-treatment ameliorates resistance to gefitinib in drug-resistant NCI-H1975 lung cancer cells. J Tradit Chin Med 2017; 37(3): 355-60.
[PMID: 31682378]
[48]
Lai KC, Chueh FS, Hsiao YT, et al. Gefitinib and curcumin-loaded nanoparticles enhance cell apoptosis in human oral cancer SAS cells in vitro and inhibit SAS cell xenografted tumor in vivo. Toxicol Appl Pharmacol 2019; 382: 114734.
[http://dx.doi.org/10.1016/j.taap.2019.114734] [PMID: 31470033]
[49]
Chen P, Huang HP, Wang Y, et al. Curcumin overcome primary gefitinib resistance in non-small-cell lung cancer cells through inducing autophagy-related cell death. J Exp Clin Cancer Res 2019; 38(1): 254.
[http://dx.doi.org/10.1186/s13046-019-1234-8] [PMID: 31196210]
[50]
Lee N, Lee K, Kim Y, et al. Combination therapy of gefitinib and Korean herbal medicines could be a beneficial option for patients with non-small-cell lung cancer. J Pharmacopuncture 2016; 19(3): 259-63.
[http://dx.doi.org/10.3831/KPI.2016.19.028] [PMID: 27695636]
[51]
Yang XB, Wu WY, Long SQ, Deng H, Pan ZQ. Effect of gefitinib plus Chinese herbal medicine (CHM) in patients with advanced non-small-cell lung cancer: A retrospective case–control study. Complement Ther Med 2014; 22(6): 1010-8.
[http://dx.doi.org/10.1016/j.ctim.2014.10.001] [PMID: 25453521]
[52]
Wang F, Wang W, Li J, Zhang J, Wang X, Wang M. Sulforaphane reverses gefitinib tolerance in human lung cancer cells via modulation of sonic hedgehog signaling. Oncol Lett 2017; 15(1): 109-14.
[http://dx.doi.org/10.3892/ol.2017.7293] [PMID: 29285189]
[53]
Zhu H, Cheng H, Ren Y, Liu ZG, Zhang YF, De Luo B. Synergistic inhibitory effects by the combination of gefitinib and genistein on NSCLC with acquired drug-resistance in vitro and in vivo. Mol Biol Rep 2012; 39(4): 4971-9.
[http://dx.doi.org/10.1007/s11033-011-1293-1] [PMID: 22160570]
[54]
Shao J, Xu Z, Peng X, et al. HeJ, Q. Gefitinib synergizes with irinotecan to suppress hepatocellular carcinoma via antagonizing Rad51-Mediated DNA-repair. PLoS One 2016; 11(1): e0146968.
[http://dx.doi.org/10.1371/journal.pone.0146968] [PMID: 26752698]
[55]
Li DC, Helal HHS, Qi CE, Zhao YY, Yao CS. The effects of combination of gefitinib and cisplatin on tongue squamous cell carcinoma cell lines. J Cancer Res Ther 2015; 11(1): 37-40.
[http://dx.doi.org/10.4103/0973-1482.147380] [PMID: 25879333]
[56]
Herbst RS, Giaccone G, Schiller JH, et al. Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: a phase III trial-INTACT 2. J Clin Oncol 2004; 22(5): 785-94.
[http://dx.doi.org/10.1200/JCO.2004.07.215] [PMID: 14990633]
[57]
Ventola CL. Cancer immunotherapy, Part 2: efficacy, safety, & other clinical considerations. P&T 2017; 42(7): 452-63.
[PMID: 28674473]
[58]
Alanazi A, Alshehri S, Altamimi M, Shakeel F. Solubility determination and three dimensional Hansen solubility parameters of gefitinib in different organic solvents: Experimental and computational approaches. J Mol Liq 2020; 299: 112211.
[http://dx.doi.org/10.1016/j.molliq.2019.112211]
[59]
Kumar CSSR. Nanotechnology tools in pharmaceutical R&D. Mater Today 2010; 12: 24-30.
[http://dx.doi.org/10.1016/S1369-7021(10)70142-5]
[60]
Truong DH, Le VKH, Pham TT, Dao AH, Pham TPD, Tran TH. Delivery of erlotinib for enhanced cancer treatment: An update review on particulate systems. J Drug Deliv Sci Technol 2020; 55: 101348.
[http://dx.doi.org/10.1016/j.jddst.2019.101348]
[61]
Singh S, Bajpai M, Mishra P. Self-Emulsifying Drug Delivery System (SEDDS): An emerging dosage form to improve the bioavailability of poorly absorbed drugs. Crit Rev Ther Drug Carrier Syst 2020; 37(4): 305-29.
[http://dx.doi.org/10.1615/CritRevTherDrugCarrierSyst.2020033111] [PMID: 32865928]
[62]
Phillip Lee YH, Sathigari S, Jean Lin YJ, et al. Gefitinib–cyclodextrin inclusion complexes: physico-chemical characterization and dissolution studies. Drug Dev Ind Pharm 2009; 35(9): 1113-20.
[http://dx.doi.org/10.1080/03639040902783074] [PMID: 19640249]
[63]
Godugu C, Doddapaneni R, Patel AR, Singh R, Mercer R, Singh M. Novel gefitinib formulation with improved oral bioavailability in treatment of A431 skin carcinoma. Pharm Res 2016; 33(1): 137-54.
[http://dx.doi.org/10.1007/s11095-015-1771-6] [PMID: 26286185]
[64]
Zhao L, Yang G, Shi Y, Su C, Chang J. Co-delivery of Gefitinib and chloroquine by chitosan nanoparticles for overcoming the drug acquired resistance. J Nanobiotechnology 2015; 13(1): 57.
[http://dx.doi.org/10.1186/s12951-015-0121-5] [PMID: 26395758]
[65]
Rizwanullah M, Ahmad J, Amin S. Nanostructured lipid carriers: A novel platform for chemotherapeutics. Curr Drug Deliv 2016; 13(1): 4-26.
[http://dx.doi.org/10.2174/1567201812666150817124133] [PMID: 26279117]
[66]
Hu Y, Zhang J, Hu H, Xu S, Xu L, Chen E. Gefitinib encapsulation based on nano-liposomes for enhancing the curative effect of lung cancer. Cell Cycle 2020; 19(24): 3581-94.
[http://dx.doi.org/10.1080/15384101.2020.1852756] [PMID: 33300430]
[67]
Gupta M, Marwaha RK, Dureja H. Development and characterization of gefitinib loaded polymeric nanoparticles by ionic gelation method. Pharm Nanotechnol 2018; 5(4): 301-9.
[http://dx.doi.org/10.2174/2211738505666171004124109] [PMID: 28982345]
[68]
Makeen HA, Mohan S, Al-Kasim MA, et al. Gefitinib loaded nanostructured lipid carriers: characterization, evaluation and anti-human colon cancer activity in vitro. Drug Deliv 2020; 27(1): 622-31.
[http://dx.doi.org/10.1080/10717544.2020.1754526] [PMID: 32329374]
[69]
Satari N, Taymouri S, Varshosaz J, Rostami M, Mirian M. Preparation and evaluation of inhalable dry powder containing glucosamine-conjugated gefitinib SLNs for lung cancer therapy. Drug Dev Ind Pharm 2020; 46(8): 1265-77.
[http://dx.doi.org/10.1080/03639045.2020.1788063] [PMID: 32594775]
[70]
Zhou X, Yung B, Huang Y, et al. Novel liposomal gefitinib (L-GEF) formulations. Anticancer Res 2012; 32(7): 2919-23.
[PMID: 22753756]
[71]
Lam ATN, Yoon J, Ganbold EO, et al. Colloidal gold nanoparticle conjugates of gefitinib. Colloids Surf B Biointerfaces 2014; 123: 61-7.
[http://dx.doi.org/10.1016/j.colsurfb.2014.08.021] [PMID: 25216919]
[72]
Bingqing D, Jianqiang H, Jianyu L. Kidney targeting nanoparticles capable of reducing gefitinib toxicity &preparation method of kidney targeting nanoparticles China Patent 112,190,565, 2021.
[73]
Jinsong X, Hao L. Method for detecting content of gefitinib in human plasma China Patent 112,198,246, 2017.
[74]
Jizhi O. Preparation &application of gefitinib idebenone conjugate Chinese patent number 11,2321,814, 2021.
[75]
Yu G, Fangyin Z, Liang X, Haijun C. Photodynamic therapy effect enhancement targeted fluorinated nanocomposite & preparation & applications thereof Fuzhou University Chinese patent 12,675,306, 2021.
[76]
Wenzhi C, Jing L, Yongkun C. Method for determining related substances of 6-acetoxy-7-methoxy-3H-quinazolin-4-one. Chinese patent 112,730,702, 2021.
[77]
Antonio M, Emilie B. Combination for treating cancer European Patent EP3,823,672, 2021.
[78]
Bell W, Haber D, Antero Janne DA, et al. Method to determine responsiveness of cancer to epidermal growth factor receptor targeting treatments. US Patent 20,210,017,604, 2021.
[79]
Huang S, Huang T, Wu M. Uses of ergosterol combined with gefitinib, preparation methods of liposome & free-dried powder thereof. US patent 0,046,090, 2021.
[80]
Johnson BE, Haber DA, Bell DW, et al. Method to determine the probability of efficacy of an EGFR tyrosine kinase inhibitor to treat cancer, use of an EGFR tyrosine kinase inhibitor, probe, kit, and, primer pair British Patent 0,508,286, 2020.
[81]
Sideng H, Wenxue X, Wei C, Aixi H, Zipeng L. Electroreduction preparation method of anticancer drug gefitinib &analogue intermediate thereof Hunan University, Zhejiang University Chinese patent 110,747,489, 2020.
[82]
Aiping W. Synthesis method of tumor cell inhibition drug Chinese Patent 110,776,471, 2020.
[83]
Sideng H, Zipeng L, Wenxue X, Xiangning H. Electroreduction preparation method of gefitinib intermediate Zhejiang University Chinese patent 110,777,391, 2020.
[84]
Chengguang Z, Lehe Y, Lingxi S. et al. Chinese patent 110,840,868, 2020.
[85]
Shengwu H, Ting H, Meijia W. Application of combination of ergosterol &gefitinib Zhejiang Chinese Medical University Chinese patent 110,882,257, 2020.
[86]
Yongzhuo H, Weimin Y. Medical composition, liposome containing medical composition & use Chinese patent 110,898,066, 2020.
[87]
Yuanyuan S, Sasa H, Yalin D, Weiyi F, Maoyi W, Ying M. Quinazolinone compounds as well as preparation method & application thereof The First Affiliated Hospital of Medical College of Xian Jiatong University Chinese patent 110,903,253, 2020.
[88]
Wen C, Dan Z, Feifei M. et al. Preparation method of gefitinib tablets. Chinese patent 111,035,619, 2020.
[89]
Zhuyong S, Zhiliang C. Preparation method of high-purity gefitinib key intermediate Chinese patent 111,039,877, 2020.
[90]
Yanbin J, Yunpeng J, Yanting W, Yang S. Pharmaceutical co-crystal of gefitinib &bumetanide &preparation method thereof Chinese patent 111,454221, 2020.
[91]
Weiliang Z, Chensheng Z, Baowang X, Xinde S, Jiayu Y, Gailan K. Purification process of gefitinib Chinese patent 111,533,703, 2020.
[92]
Guimin Z, Lihong G, Lihai Z, Mingming Z. 2020.Gefitinib & 3-hydroxyl benzoic acid eutectic crystal. Chinese Patent 112,047,892,
[93]
Guimin Z, Zhong L, Lihai Z, Mingming Z. Gefitinib & salicylic acid eutectic crystal Chinese Patent 112,047,893, 2020.
[94]
Lihai Z, Xiuyan X, Junhou Y, Chao M. Gefitinib and vanillic acid co-crystal methanol solvate and preparation method thereof Chinese patent 112,142,679, 2020.
[95]
Chuanwei Y, Yingchao X, Hui Z, Dalei K, Wenwen C, Juntao L. Vacuum drying device for gefitinib production Chinese patent 211,041,597, 2020.
[96]
Chuanwei Y, Yingchao X, Hui Z, Dalei K, Wenwen C, Juntao L. Filter pressing device for gefitinib production Chinese patent 211,357,857, 2020.
[97]
Bo Y, Tongjun D. Novel reaction device for gefitinib nitration process Chinese Patent 211,586,590, 2020.
[98]
Ballestrero A, Irene C, Longo V, Nencioni A, Patrizio D, Patrone F. Tyrosine kinase inhibitor used in cancer treatment in collaboration with reduced caloric intake Japanese Patent 2020,147,598, 2020.
[99]
Tiedt R, Chatenay-Rivauday C, Moriko I, Bin P, Ying G, Akimov M. Combination products with tyrosine kinase inhibitors & uses thereof Japanese patent JP2020172504, 2020.
[100]
Woohn KD, Ruem BA. Pharmaceutical composition containing keratin-8-phosphorylation inhibitor for preventing or treating macular degeneration & method for screening macular degeneration medicine Japanese patent 2020,196,734, 2020.
[101]
Jennifer S, Brian P. Tumor targeting Vitamin B12 derivatives for X-ray activated chemotherapy. Worldwide patent 2020.113,130, 2020.
[102]
Piaoyang S, Quanren W, Shaorong L, Lei Z. Method for reducing clinical toxicity of apatinib Worldwide patent 2,020,233579, 2020.

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