标靶治疗

标靶治疗或标靶分子治療（英語：Targeted Therapy、Molecularly Targeted Therapy）是一種以干擾癌變或腫瘤增生所需的特定分子來阻止癌細胞增長的一種藥物療法，^[1]而非一般的干擾所有持續分裂細胞（不穩定細胞）的傳統化療法。放射療法儘管是針對特定腫瘤的，但是並非此處「标靶」的含義。

癌症标靶治疗在被認為是比當今其他療法更加有效，並且對正常細胞傷害更小的療法。

标靶治疗可以治療乳腺癌、多發性骨髓瘤，淋巴癌，前列腺癌，黑色素瘤, 甲狀腺癌以及其他一些癌症。^[2] ^[3]

Mark Greene在1985年報告，確切的實驗（在體內和體外環境用單株抗體處理Her2/neu軟化細胞）表明标靶治疗會逆轉腫瘤細胞惡性表型。^[4]

一些人拒絕接受标靶治疗這個術語所指的藥物是沒有選擇性的這種觀點。^[5]「标靶治疗」這個術語有時在文章中，會帶雙引號出現。^[6]

種類

标靶治疗可分為小分子，小分子偶聯物，單株抗體三大類。

小分子

大多是酪氨酸激酶抑制劑 (TKI)。

甲磺酸伊馬替尼 (格列衛，或STI–571)被批准用於慢性髓細胞性白血病，胃腸道間質瘤以及其他一些癌症。早期的臨床試驗表明，伊馬替尼對皮膚纖維肉瘤的治療有效。
吉非替尼 (易瑞沙，或ZD1839)針對表皮生長因子酪氨酸激酶，在美國被批准用於非小細胞肺癌。
厄洛替尼 (特羅凱)與吉非替尼機理類似，抑制表皮生長因子。^[7]厄洛替尼在二線治療中被顯示提高了轉移性非小細胞肺癌患者的存活率。因此厄洛替尼在此方面代替了吉非替尼。
硼替佐米 (萬珂)是一種誘導細胞凋亡蛋白酶抑制劑。這種藥能干擾癌細胞蛋白質並使之死亡。它在美國被批准用以治療多發性骨髓瘤，但沒有用在其他方面的治療。
選擇性雌性激素受體調節劑三苯氧胺是标靶治疗的第一種藥品。^[8]
JAK激酶抑制劑如FDA批准的托法替尼。
間變性淋巴瘤激酶抑制劑如克唑替尼
B細胞淋巴瘤-2抑制劑如ABT-263以及棉酚.^[9]
聚ADP核糖聚合酶抑制劑如在一次臨床試驗中的Iniparib 奧拉帕尼
磷脂酰肌醇三激酶抑制劑如在一次三期臨床試驗中的哌立福辛
阿帕替尼是一種選擇性血管內皮細胞生長因子受體2抑制劑，臨床試驗中，它表現出了廣泛的抗癌性。^[10]阿帕替尼目前在臨床開發中用於轉移性胃癌，轉移性乳腺癌以及晚期肝細胞肝癌。^[11]
AN-152, (AEZS-108) 阿黴素結合[D-Lys(6)]- LHRH, 階段II用以治療卵巢癌^[12]
Braf抑制劑 (維羅非尼，達拉菲尼，LGX818)用以治療帶有BRAF V600E突變的轉移性黑色素瘤。
裂原活化蛋白激酶抑制劑(trametinib, MEK162)經常在實驗中與BRAF抑制劑一同使用以治療黑色素瘤。
周期蛋白依賴性激酶抑制劑如PD-0332991, LEE011被用於臨床試驗。
熱休克蛋白90抑制劑被用於臨床試驗
沙利黴素在自然和實驗室創造的小鼠乳腺癌中展現出了殺死腫瘤幹細胞的效力。

小分子偶聯物

Vintafolide是一種針對葉酸受體的小分子偶聯物。目前被用於鉑類耐藥性卵巢癌，以及在非小細胞肺癌的第2b期研究。^[13]

單株抗體

一些單株抗體正在發展，少數已獲得FDA的批准。以下是一些得到許可的單株抗體：

利妥昔單抗 (美羅華或瑞圖宣)針對B淋巴細胞抗原CD20，被用於非霍奇金淋巴瘤。
曲妥單抗 (赫塞汀)針對在某些乳腺癌中的Her2/neu(或稱ErbB2)受體。
西妥昔單抗 (愛必妥)針對表皮生長因子受體。被用於治療結腸癌和非小細胞肺癌。
貝伐單抗 ( 阿瓦斯丁)針對環血管內皮生長因子配位體。被許可用於結腸癌，乳腺癌，非小細胞肺癌。並有治療肉瘤的臨床試驗。並被推薦用以治療腦瘤

有許多抗體偶聯物正在研發，請參見抗體導向酶前藥治療 (ADEPT)。

進展與未來發展

在美國，美國國家癌症研究所分子标靶發展計劃（Molecular Targets Development Program]，MTDP）致力於研究可能對藥物發展有幫助的分子标靶。

參見

參考文獻

↑ Definition of targeted therapy - NCI Dictionary of Cancer Terms.
↑ NCI: Targeted Therapy tutorials
↑ 甲狀腺癌復發-标靶治疗解困局
↑ Perantoni AO, Rice JM, Reed CD, Watatani M, Wenk ML. Activated neu oncogene sequences in primary tumors of the peripheral nervous system induced in rats by transplacental exposure to ethylnitrosourea. Proc. Natl. Acad. Sci. U.S.A. 1987-09, 84 (17): 6317–6321. PMC 299062 . PMID 3476947. doi:10.1073/pnas.84.17.6317.
Drebin JA, Link VC, Weinberg RA, Greene MI. Inhibition of tumor growth by a monoclonal antibody reactive with an oncogene-encoded tumor antigen. Proc. Natl. Acad. Sci. U.S.A. 1986-12, 83 (23): 9129–9133. PMC 387088 . PMID 3466178. doi:10.1073/pnas.83.23.9129.
Drebin JA, Link VC, Stern DF, Weinberg RA, Greene MI. Down-modulation of an oncogene protein product and reversion of the transformed phenotype by monoclonal antibodies. Cell. 1985-07, 41 (3): 697–706. PMID 2860972. doi:10.1016/S0092-8674(85)80050-7.
↑ Zhukov NV, Tjulandin SA. Targeted therapy in the treatment of solid tumors: practice contradicts theory. Biochemistry Mosc. 2008-05, 73 (5): 605–618. PMID 18605984. doi:10.1134/S000629790805012X.
↑ Markman M. The promise and perils of 'targeted therapy' of advanced ovarian cancer. Oncology. 2008, 74 (1–2): 1–6. PMID 18536523. doi:10.1159/000138349.
↑ Katzel JA, Fanucchi MP, Li Z. Recent advances of novel targeted therapy in non-small cell lung cancer. J Hematol Oncol. 2009-01, 2 (1): 2. PMC 2637898 . PMID 19159467. doi:10.1186/1756-8722-2-2.
↑ Jordan VC. Tamoxifen: catalyst for the change to targeted therapy. Eur. J. Cancer. 2008-01, 44 (1): 30–38. PMC 2566958 . PMID 18068350. doi:10.1016/j.ejca.2007.11.002.
↑ Warr MR, Shore GC. Small-molecule Bcl-2 antagonists as targeted therapy in oncology. Curr Oncol. 2008-12, 15 (6): 256–61 [2013-12-15]. PMC 2601021 . PMID 19079626.
↑ Li J, Zhao X, Chen L; et al. Safety and pharmacokinetics of novel selective vascular endothelial growth factor receptor-2 inhibitor YN968D1 in patients with advanced malignancies. BMC Cancer. 2010, 10: 529. PMC 2984425 . PMID 20923544. doi:10.1186/1471-2407-10-529.
↑ 存档副本. [2013-12-15].
↑ Phase II study of AEZS-108 (AN-152), a targeted cytotoxic LHRH analog, in patients with LHRH receptor-positive platinum resistant ovarian cancer.. 2010 [2013-12-15].
↑ Merck, Endocyte in Development Deal - Drug Discovery and Development

外部連結

CancerDriver : a free and open database to find targeted therapies according to the patient's features.
Targeted Therapy Database (TTD) [1] from the Melanoma Molecular Map Project [2]
Targeted therapy Fact sheet from the U.S. National Cancer Institute
Molecular Oncology: Receptor-Based Therapy Special issue of Journal of Clinical Oncology (April 10, 2005) dedicated to targeted therapies in cancer treatment
Targeting Targeted Therapy New England Journal of Medicine (2004)
Targeting tumors with medicinal cannabis oil - publication list from Spain
財團法人台灣癌症基金會-什麼是标靶治疗?

[NCI-TT-def-1] Definition of targeted therapy - NCI Dictionary of Cancer Terms.

[NCI-TT-tutorials-2] NCI: Targeted Therapy tutorials

[MEDcentra-3] 甲狀腺癌復發-标靶治疗解困局

[4] Perantoni AO, Rice JM, Reed CD, Watatani M, Wenk ML. Activated neu oncogene sequences in primary tumors of the peripheral nervous system induced in rats by transplacental exposure to ethylnitrosourea. Proc. Natl. Acad. Sci. U.S.A. 1987-09, 84 (17): 6317–6321. PMC 299062 . PMID 3476947. doi:10.1073/pnas.84.17.6317.
Drebin JA, Link VC, Weinberg RA, Greene MI. Inhibition of tumor growth by a monoclonal antibody reactive with an oncogene-encoded tumor antigen. Proc. Natl. Acad. Sci. U.S.A. 1986-12, 83 (23): 9129–9133. PMC 387088 . PMID 3466178. doi:10.1073/pnas.83.23.9129.
Drebin JA, Link VC, Stern DF, Weinberg RA, Greene MI. Down-modulation of an oncogene protein product and reversion of the transformed phenotype by monoclonal antibodies. Cell. 1985-07, 41 (3): 697–706. PMID 2860972. doi:10.1016/S0092-8674(85)80050-7.

[pmid18605984-5] Zhukov NV, Tjulandin SA. Targeted therapy in the treatment of solid tumors: practice contradicts theory. Biochemistry Mosc. 2008-05, 73 (5): 605–618. PMID 18605984. doi:10.1134/S000629790805012X.

[pmid18536523-6] Markman M. The promise and perils of 'targeted therapy' of advanced ovarian cancer. Oncology. 2008, 74 (1–2): 1–6. PMID 18536523. doi:10.1159/000138349.

[pmid19159467-7] Katzel JA, Fanucchi MP, Li Z. Recent advances of novel targeted therapy in non-small cell lung cancer. J Hematol Oncol. 2009-01, 2 (1): 2. PMC 2637898 . PMID 19159467. doi:10.1186/1756-8722-2-2.

[pmid18068350-8] Jordan VC. Tamoxifen: catalyst for the change to targeted therapy. Eur. J. Cancer. 2008-01, 44 (1): 30–38. PMC 2566958 . PMID 18068350. doi:10.1016/j.ejca.2007.11.002.

[pmid19079626-9] Warr MR, Shore GC. Small-molecule Bcl-2 antagonists as targeted therapy in oncology. Curr Oncol. 2008-12, 15 (6): 256–61 [2013-12-15]. PMC 2601021 . PMID 19079626.

[10] Li J, Zhao X, Chen L; et al. Safety and pharmacokinetics of novel selective vascular endothelial growth factor receptor-2 inhibitor YN968D1 in patients with advanced malignancies. BMC Cancer. 2010, 10: 529. PMC 2984425 . PMID 20923544. doi:10.1186/1471-2407-10-529.

[11] 存档副本. [2013-12-15].

[12] Phase II study of AEZS-108 (AN-152), a targeted cytotoxic LHRH analog, in patients with LHRH receptor-positive platinum resistant ovarian cancer.. 2010 [2013-12-15].

[13] Merck, Endocyte in Development Deal - Drug Discovery and Development

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]

[10]

[11]

[12]

[13]