晚期非小细胞肺癌靶向治疗的研究进展

姜文丽; 黄才国

doi:10.3969/j.issn.1006-0111.2016.04.004

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晚期非小细胞肺癌靶向治疗的研究进展

姜文丽, 黄才国

文章导航 > 药学实践与服务 > 2016 > 34(4): 301-304,333

姜文丽, 黄才国. 晚期非小细胞肺癌靶向治疗的研究进展[J]. 药学实践与服务, 2016, 34(4): 301-304,333. doi: 10.3969/j.issn.1006-0111.2016.04.004

引用本文:

姜文丽, 黄才国. 晚期非小细胞肺癌靶向治疗的研究进展[J]. 药学实践与服务, 2016, 34(4): 301-304,333. doi: 10.3969/j.issn.1006-0111.2016.04.004

JIANG Wenli, HANG Caiguo. Research progress on target therapy of advanced non-small cell lung cancer[J]. Journal of Pharmaceutical Practice and Service, 2016, 34(4): 301-304,333. doi: 10.3969/j.issn.1006-0111.2016.04.004

Citation:

JIANG Wenli, HANG Caiguo. Research progress on target therapy of advanced non-small cell lung cancer[J]. Journal of Pharmaceutical Practice and Service, 2016, 34(4): 301-304,333. doi: 10.3969/j.issn.1006-0111.2016.04.004

晚期非小细胞肺癌靶向治疗的研究进展

doi: 10.3969/j.issn.1006-0111.2016.04.004

第二军医大学基础部生物化学与分子生物学教研室, 上海 200433

基金项目: 国家自然科学基金面上项目（41576160，81473239）

Research progress on target therapy of advanced non-small cell lung cancer

Department of Biochemistry and Molecular Biology, Faculty of Basic Medicine, Second Military Medical University, Shanghai 200433, China

摘要: 生物标志物检测使得许多晚期非小细胞肺癌（NSCLC）患者获益。近年来，针对表皮生长因子受体（EGFR）和间变性淋巴瘤激酶（ALK）突变呈阳性的NSCLC患者，以吉非替尼、厄洛替尼、阿法替尼为代表的表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）和以克唑替尼为代表的ALK-TKI取得了卓越的疗效。但是，大多数第一代EGFR-TKI和ALK-TKI的疗效因为不可避免的继发性耐药而被减弱。目前，第三代EGFR-TKI正是基于第二代EGFR-TKI的耐药机制研发而成。除此之外，还有许多针对其他突变位点的晚期NSCLC维持治疗的靶向抑制剂。遗憾的是，针对突变比例最大的K-RAS突变，尚无疗效确切的靶向药物。因此，基于肿瘤驱动基因突变机制的探索和靶向药物的开发是目前NSCLC的研究热点。
- 非小细胞肺癌 /
- 靶向药物 /
- 肿瘤
Abstract: Detection of biomarkers benefited many advanced non-small cell lung cancer (NSCLC) patients. In recent years, epidermal growth factor (EGFR) tyrosine kinase inhibitors (TKIs) represented by Gefitinib, Erlotinib, Afatinib and anaplastic lymphoma kinase (ALK) TKIs represented by Crizotinib have remarkable efficacy. However, the efficacy for most first-generation EGFR-TKI and ALK-TKI is weakened due to secondary resistance. Currently, the third-generation EGFR-TKI which successfully against drug resistance is based on research and development of the second-generation. In addition, there are many other targeted inhibitors of mutation sites for advanced NSCLC. Unfortunately, the largest proportion of Kirsten rat sarcoma viral oncogene homolog (K-RAS) mutation is not targetable with small molecule inhibitors currently. Therefore, based on mechanisms exploration of tumor driven gene mutation, its target drug research and development will be greatly addressed in the future.
- non-small cell lung cancer (NSCLC) /
- molecular targeting agents /
- tumour

[1]	Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015[J]. CA Cancer J Clin, 2016,66(2):115-132.
[2]	Jorge S, Kobayashi SS, Costa DB. Epidermal growth factor receptor (EGFR) mutations in lung cancer:preclinical and clinical data[J]. Brazil J Med Biolog Res, 2014,47(11):929-939.
[3]	Sequist LV, Yang JC, Yamamoto N, et al. Phase Ⅲ study of Afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations[J]. J Clin Oncol, 2013, 31(27):3327-3334.
[4]	Banno E, Togashi Y, Kobayashi Y, et al. Afatinib is especially effective against non-small cell lung cancer carrying an EGFR exon 19 deletion[J]. Anticancer Res, 2015,35(4):2005-2008.
[5]	Karachaliou N, Mayo-de las Casas C, Queralt C, et al. Association of EGFR L858R mutation in circulating free DNA with survival in the EURTAC trial[J]. JAMA Oncol, 2015,1(2):149-157.
[6]	Sadek M, Alexakis A, Fauve S. OPTIMAL length scale for a turbulent dynamo[J]. Phys Rev Lett, 2016, 116(7):074501.
[7]	Choi SH, Mendrola JM, Lemmon MA. EGF-independent activation of cell-surface EGF receptors harboring mutations found in Gefitinib-sensitive lung cancer[J]. Oncogene, 2007, 26(11):1567-1576.
[8]	Steuer CE, Ramalingam SS. Targeting EGFR in lung cancer:Lessons learned and future perspectives[J]. Mol Aspects Med, 2015, 45:67-73.
[9]	Vacondio F, Carmi C, Galvani E, et al. Long-lasting inhibition of EGFR autophosphorylation in A549 tumor cells by intracellular accumulation of non-covalent inhibitors[J]. Bioorg Med Chem Lett, 2013, 23(19):5290-5294.
[10]	Giordano P, Manzo A, Montanino A, et al. Afatinib:An overview of its clinical development in non-small-cell lung cancer and other tumors[J]. Crit Rev Oncol Hematol, 2016, 97:143-151.
[11]	Kato T, Yoshioka H, Okamoto I, et al. Afatinib versus cisplatin plus pemetrexed in Japanese patients with advanced non-small cell lung cancer harboring activating EGFR mutations:Subgroup analysis of LUX-Lung 3[J]. Cancer Sci, 2015, 106(9):1202-1211.
[12]	Soria JC, Felip E, Cobo M, et al. Afatinib versus Erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8):an open-label randomised controlled phase 3 trial[J]. Lancet Oncol, 2015, 16(8):897-907.
[13]	Janne PA, Yang JC, Kim DW, et al. AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer[J]. N Engl J Med, 2015, 372(18):1689-1699.
[14]	Greig SL. Osimertinib:First global approval[J]. Drugs, 2016, 76(2):263-273.
[15]	Shea M, Costa DB, Rangachari D. Management of advanced non-small cell lung cancers with known mutations or rearrangements:Latest evidence and treatment approaches[J]. Ther Adv Respir Dis, 2016, 10(2):113-129.
[16]	Yu HA, Arcila ME, Rekhtman N, et al. Analysis of tumor specimens at the time of acquired resistance to EGFR-TKI therapy in 155 patients with EGFR-mutant lung cancers[J]. Clin Cancer Res, 2013, 19(8):2240-2247.
[17]	Chong CR, Janne PA. The quest to overcome resistance to EGFR-targeted therapies in cancer[J]. Nat Med, 2013,19(11):1389-1400.
[18]	Li D, Ambrogio L, Shimamura T, et al. BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models[J]. Oncogene, 2008, 27(34):4702-4711.
[19]	Soda M, Choi YL, Enomoto M, et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer[J]. Nature, 2007, 448(7153):561-566.
[20]	Cameron L, Solomon B. New treatment options for ALK-rearranged non-small cell lung cancer[J]. Curr Treat Options Oncol, 2015, 16(10):49.
[21]	Costa DB, Shaw AT, Ou SH, et al. Clinical experience with crizotinib in patients with advanced ALK-rearranged non-small-cell lung cancer and brain metastases[J]. J Clin Oncol, 2015,33(17):1881-1888.
[22]	Lukas RV, Hasan Y, Nicholas MK, et al. ROS1 rearranged non-small cell lung cancer brain metastases respond to low dose radiotherapy[J]. J Clin Neurosci, 2015,22(12):1978-1979.
[23]	Marchetti A, Felicioni L, Malatesta S, et al. Clinical features and outcome of patients with non-small-cell lung cancer harboring BRAF mutations[J]. J Clin Oncol,2011,29(26):3574-3579.
[24]	石远凯,孙燕,于金明,等.中国晚期原发性肺癌诊治专家共识(2016年版)[J].中国肺癌杂志,2016,19(1):1-15.
[25]	Lipson D, Capelletti M, Yelensky R, et al. Identification of new ALK and RET gene fusions from colorectal and lung cancer biopsies[J]. Nat Med, 2012, 18(3):382-384.
[26]	Li BT, Ross DS, Aisner DL, et al. HER2 amplification and HER2 mutation are distinct molecular targets in lung cancers[J]. J Thorac Oncol, 2016, 11(3):414-419.
[27]	Mar N, Vredenburgh JJ, Wasser JS. Targeting HER2 in the treatment of non-small cell lung cancer[J]. Lung Cancer, 2015, 87(3):220-225.

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晚期非小细胞肺癌靶向治疗的研究进展

doi: 10.3969/j.issn.1006-0111.2016.04.004

第二军医大学基础部生物化学与分子生物学教研室, 上海 200433

基金项目: 国家自然科学基金面上项目（41576160，81473239）

收稿日期: 2016-01-26
修回日期: 2016-03-25

关键词:

非小细胞肺癌 /

靶向药物 /

肿瘤

摘要: 生物标志物检测使得许多晚期非小细胞肺癌（NSCLC）患者获益。近年来，针对表皮生长因子受体（EGFR）和间变性淋巴瘤激酶（ALK）突变呈阳性的NSCLC患者，以吉非替尼、厄洛替尼、阿法替尼为代表的表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）和以克唑替尼为代表的ALK-TKI取得了卓越的疗效。但是，大多数第一代EGFR-TKI和ALK-TKI的疗效因为不可避免的继发性耐药而被减弱。目前，第三代EGFR-TKI正是基于第二代EGFR-TKI的耐药机制研发而成。除此之外，还有许多针对其他突变位点的晚期NSCLC维持治疗的靶向抑制剂。遗憾的是，针对突变比例最大的K-RAS突变，尚无疗效确切的靶向药物。因此，基于肿瘤驱动基因突变机制的探索和靶向药物的开发是目前NSCLC的研究热点。