癌癥靶向治療藥物綜述    
2017年05月02日
標簽:
對此內容提問

目錄

Overview of Targeted Therapies for Cancer

Targeted cancer therapies are drugs designed to interfere with specific molecules necessary for tumor growth and progression. Traditional cytotoxic chemotherapies usually kill rapidly dividing cells in the body by interfering with cell division. A primary goal of targeted therapies is to fight cancer cells with more precision and potentially fewer side effects.

靶向癌癥治療方法是藥物設計上即精準針對在腫瘤發生和生長中作為必要條件的特定分子進行干擾。傳統的細胞毒藥物治療通常是通過干擾細胞分裂,滅殺體內快速分裂的細胞。靶向治療的首要目標是盡最大可能針對殺滅癌細胞,同時盡可能避免潛在的副作用。

Classification and naming

分類和命名

Targeted cancer agents are broadly classified as either monoclonal antibodies or small molecules.

靶向抗癌藥粗略可以分為單克隆抗體和小分子化合物

Therapeutic monoclonal antibodies target specific antigens found on the cell surface, such as transmembranereceptorsor extracellular growth factors. In some cases, monoclonal antibodies are conjugated to radio-isotopes or toxins to allow specific delivery of these cytotoxic agents to the intended cancer cell target.

單克隆抗體治療靶點是基于細胞表面的特殊抗原,比如跨膜受體或細胞外生長因子。在某些情況下,單克隆抗體結合放射性同位素或毒素允許基因定位轉運這些細胞毒藥物到達選定的癌細胞靶點。

Small molecules can penetrate the cell membrane to interact with targets inside a cell. Small molecules are usually designed to interfere with the enzymatic activity of the targetprotein.

As with any drug, targeted cancer therapies typically have several different names. One or more names is used to designate the chemical compound during development; if successful, the drug receives a generic name and then a brand name used by the pharmaceutical company for marketing. For example, the small molecule STI-571 became known as imatinib (generic name) and is marketed by Novartis under the brand name Gleevec?.

小分子化合物能夠穿透細胞膜,與細胞內的一個靶點產生相互作用。小分子化合物通常旨在干擾靶蛋白的酶活性。與其他藥物一樣,靶向癌癥治療藥物通常在藥物研發過程中有幾個不同的名字,一般習慣會給化合物指定一個或多個名稱。如果研發成功,這個小分子化合物會得到一個通用名和一個制藥公司用于銷售的商品品牌名稱。例如,小分子化合物STI-571被稱為伊馬替尼(通用名稱),諾華制藥公司銷售的藥物品牌名稱是Gleevec?.(格列衛?)。

The name of a targeted agent provides clues to the type of agent and its cellular target.

藥物靶點的命名要求標示靶點的類型和它們針對的細胞靶點。

Monoclonal antibodies end with the stem “-mab” (monoclonal antibody). Small molecules end with the stem “-ib” (indicating that the agent has proteininhibitory properties). Monoclonal antibodies have an additional substem designating the source of the compound, e.g., “-ximab” for chimeric human-mouse antibodies, “-zumab” for humanized mouse antibodies, and “-mumab” for fully human antibodies. Both monoclonal antibodies and small molecules contain an additional stem in the middle of the name describing the molecule’s target; examples for monoclonal antibodies include “-ci-” for a circulatory system target and “-tu-” for a tumor target, while examples for small molecules include “-tin-” for tyrosinekinase inhibitors and “-zom-” for proteasome inhibitors. At the beginning of the generic name is a prefix that is unique for each agent. Some examples include:

單克隆抗體名稱后綴“-mab”(單克隆抗體)。小分子化合物名稱后綴 “-ib”(提示目標靶點有蛋白質抑制特性)。單克隆抗體有一個附加的詞綴,表明來源不同,例如“-ximab”是人-鼠嵌合抗體。”-zumab” 人源化抗體,”-mumab” 是全人源化抗體。單克隆抗體和小分子化合物都含有一個附加的詞綴,在名字中描述分子的靶點;例如單克隆抗體包含“-ci-”針對循環系統靶點,“-tu-”針對腫瘤靶點,小分子化合物包含“-tin-”表明是酪氨酸激酶抑制劑,“-zom-”表明是蛋白酶體抑制劑。每個靶向藥物通用名稱開頭的前綴都是獨一無二的。下面舉例說明:

Monoclonal antibodies 單克隆抗體
bevacizumabhumanized monoclonal antibodywith a circulatory system target (VEGF-A) 以循環系統為靶點的人源化單克隆抗體(血管內生長因子)
cetuximabchimeric monoclonal antibody with a tumor target (EGFR) 以腫瘤為靶點的嵌合單克隆抗體(表皮生長因子受體)
ipilimumabfully human antibody with animmune system target (CTLA-4) 以免疫系統為靶點的全人源抗體 (CTLA-4 細胞毒性淋巴細胞抗原)
Small molecules 小分子化合物
bortezomibsmall molecule proteasome inhibitor 小分子蛋白酶體抑制劑
imatinibsmall molecule tyrosine kinase inhibitor 小分子酪氨酸激酶抑制劑
seliciclibsmall molecule cyclin-dependent kinase inhibitor 小分子細胞周期蛋白依賴性激酶抑制劑

The FDA has approved multiple targeted drug cancer therapies, and many more are being studied in clinical trials either alone or in combination with other treatments. A partial list of currently approved targeted therapies for solid malignancies and their molecular targets is provided below.

FDA已經批準了多種癌癥的靶向治療藥物臨床使用,以及更多的單獨或聯合其他治療的靶向藥物臨床試驗。下表是目前批準的部分名單,靶向治療針對難治的惡性腫瘤及其分子靶點。

Agent 藥名Target(s) 靶點FDA-approved indication(s) 適用范圍
Ado-trastuzumab emtansine (Kadcyla)HER2 (ERBB2/neu)· Breast cancer乳腺癌 (HER2+)
Afatinib (Gilotrif)EGFR (HER1/ERBB1), HER2 (ERBB2/neu)· Non-small cell lung cancer非小細胞肺癌 (with EGFR exon 19 deletions or exon 21 substitution (L858R) mutations)
Aldesleukin (Proleukin)
· Renal cell carcinoma 腎細胞癌 · Melanoma 黑色素瘤
Alectinib (Alecensa)ALK· Non-small cell lung cancer非小細胞肺癌(with ALK fusion)
Alemtuzumab (Campath)CD52· B-cell chronic lymphocytic leukemia 細胞慢性淋巴細胞白血病
Axitinib (Inlyta)KIT, PDGFRβ, VEGFR1/2/3· Renal cell carcinoma腎細胞癌
Belimumab (Benlysta)BAFF· Lupus erythematosus 紅斑狼瘡
Belinostat (Beleodaq)HDAC· Peripheral T-cell lymphoma 外周T細胞淋巴瘤
Bevacizumab (Avastin)VEGF ligand· Cervical cancer 宮頸癌 · Colorectal cancer 大腸癌 · Fallopian tube cancer 輸卵管癌 · Glioblastoma 膠質母細胞瘤 · Non-small cell lung cancer 非小細胞肺癌 · Ovarian cancer 卵巢癌 · Peritoneal cancer 腎細胞癌 · Renal cell carcinoma 腹膜癌
Bortezomib (Velcade)Proteasome· Multiple myeloma 多發性骨髓瘤 · Mantle cell lymphoma 套細胞淋巴瘤
Bosutinib (Bosulif)ABL· Chronic myelogenous leukemia 慢性粒細胞性白血病(Philadelphia chromosomepositive)
Brentuximab vedotin (Adcetris)CD30· Hodgkin lymphoma 霍奇金淋巴瘤 · Anaplastic large cell lymphoma 間變性大細胞淋巴瘤
Cabozantinib (Cabometyx [tablet], Cometriq [capsule])FLT3, KIT, MET, RET, VEGFR2· Medullary thyroid cancer 甲狀腺髓樣癌 · Renal cell carcinoma 腎細胞癌
Canakinumab (Ilaris)IL-1β· Juvenile idiopathic arthritis 青少年特發性關節炎 · Cryopyrin-associated periodic syndromes
Carfilzomib (Kyprolis)Proteasome· Multiple myeloma 多發性骨髓瘤
Ceritinib (Zykadia)ALK· Non-small cell lung cancer 非小細胞肺癌(with ALK fusion)
Cetuximab (Erbitux)EGFR (HER1/ERBB1)· Colorectal cancer 大腸癌 (KRAS wild type) · Squamous cell cancer of the head and neck頭頸部鱗狀細胞癌
Cobimetinib (Cotellic)MEK· Melanoma 黑色素瘤 (with BRAF V600E or V600K mutation)
Crizotinib (Xalkori)ALK, MET, ROS1· Non-small cell lung cancer 非小細胞肺癌 (with ALK fusion or ROS1 genealteration)
Dabrafenib (Tafinlar)BRAF· Melanoma 黑色素瘤 (with BRAF V600 mutation)
Daratumumab (Darzalex)CD38· Multiple myeloma 多發性骨髓瘤
Dasatinib (Sprycel)ABL· Chronic myelogenous leukemia 慢性粒細胞白血病(Philadelphia chromosomepositive) · Acute lymphoblastic leukemia 急性淋巴細胞白血病(Philadelphia chromosomepositive)
Denosumab (Xgeva)RANKL· Giant cell tumor of the bone 骨巨細胞瘤
Dinutuximab (Unituxin)B4GALNT1 (GD2)· Pediatric neuroblastoma 小兒神經母細胞瘤
Elotuzumab (Empliciti)SLAMF7 (CS1/CD319/CRACC)· Multiple myeloma 多發性骨髓瘤
Erlotinib (Tarceva)EGFR (HER1/ERBB1)· Non-small cell lung cancer 非小細胞肺癌 · Pancreatic cancer 胰腺癌
Everolimus (Afinitor)mTOR· Pancreatic, gastrointestinal, or lung origin neuroendocrine tumor 起源于胰、腸胃或肺的神經內分泌腫瘤 · Renal cell carcinoma 腎細胞癌 · Nonresectable subependymal giant cell astrocytoma associated with tuberous sclerosis不可切除的室管膜下巨細胞星狀細胞瘤關聯的結節性硬化癥 · Breast cancer 乳腺癌 (HR+, HER2-)
Gefitinib (Iressa)EGFR (HER1/ERBB1)· Non-small cell lung cancer 非小細胞肺癌 (with EGFR exon 19 deletions or exon 21 substitution (L858R) mutations)
Ibritumomab tiuxetan (Zevalin)CD20· Non-Hodgkin’s lymphoma 非霍奇金淋巴瘤
Ibrutinib (Imbruvica)BTK· Mantle cell lymphoma 套細胞淋巴瘤 · Chronic lymphocytic leukemia 慢性淋巴細胞白血病 · Waldenstrom’s macroglobulinemia 巨球蛋白血癥
Idelalisib (Zydelig)PI3Kδ· Chronic lymphocytic leukemia慢性淋巴細胞白血病 · Follicular B-cell non-Hodgkin lymphoma 卵泡B細胞非霍奇金淋巴瘤 · Small lymphocytic lymphoma 小淋巴細胞淋巴瘤
Imatinib (Gleevec)KIT, PDGFR, ABL· GI stromal tumor (KIT+)胃腸道間質瘤 · Dermatofibrosarcoma protuberans 隆突性皮纖維肉瘤 · Multiple hematologic malignancies including Philadelphia chromosome-positive ALL and CML
Ipilimumab (Yervoy)CTLA-4· Melanoma 黑色素瘤
Ixazomib (Ninlaro)Proteasome· Multiple Myeloma 多發性骨髓瘤
Lapatinib (Tykerb)HER2 (ERBB2/neu), EGFR(HER1/ERBB1)· Breast cancer 乳腺癌(HER2+)
Lenvatinib (Lenvima)VEGFR2· Thyroid cancer 甲狀腺癌
Necitumumab (Portrazza)EGFR (HER1/ERBB1)· Squamous non-small cell lung cancer 鱗狀非小細胞肺癌
Nilotinib (Tasigna)ABL· Chronic myelogenous leukemia 慢性粒細胞性白血病(Philadelphia chromosomepositive)
Nivolumab (Opdivo)PD-1· Melanoma黑色素瘤 · Non-small cell lung cancer 非小細胞肺癌 · Renal cell carcinoma 腎細胞癌
Obinutuzumab (Gazyva)CD20· Chronic lymphocytic leukemia 慢性淋巴細胞白血病 · Follicular lymphoma 卵泡淋巴瘤
Ofatumumab (Arzerra, HuMax-CD20)CD20· Chronic lymphocytic leukemia 慢性淋巴細胞白血病
Olaparib (Lynparza)PARP· Ovarian cancer 卵巢癌 (with BRCA mutation)
Osimertinib (Tagrisso)EGFR· Non-small cell lung cancer 非小細胞肺癌 (with EGFR T790M mutation)
Palbociclib (Ibrance)CDK4, CDK6· Breast cancer 乳腺癌 (ER+, HER2-)
Panitumumab (Vectibix)EGFR (HER1/ERBB1)· Colorectal cancer 大腸癌(KRAS wild type)
Panobinostat (Farydak)HDAC· Multiple myeloma 多發性骨髓瘤
Pazopanib (Votrient)VEGFR, PDGFR, KIT· Renal cell carcinoma 腎細胞癌
Pembrolizumab (Keytruda)PD-1· Melanoma 黑色素瘤 · Non-small cell lung cancer 非小細胞肺癌 (PD-L1+)
Pertuzumab (Perjeta)HER2 (ERBB2/neu)· Breast cancer 乳腺癌(HER2+)
Ponatinib (Iclusig)ABL, FGFR1-3, FLT3, VEGFR2· Chronic myelogenous leukemia 慢性粒細胞性白血病 · Acute lymphoblastic leukemia 急性淋巴細胞白血病 (Philadelphia chromosomepositive)
Ramucirumab (Cyramza)VEGFR2· Colorectal cancer 大腸癌 · Gastric cancer or Gastroesophageal junction (GEJ) adenocarcinoma 胃癌或胃食管交界處(GEJ)腺癌 · Non-small cell lung cancer 非小細胞肺癌
Regorafenib (Stivarga)KIT, PDGFRβ, RAF, RET, VEGFR1/2/3· Colorectal cancer 大腸癌 · Gastrointestinal stromal tumors 胃腸間質瘤
Rituximab (Rituxan, Mabthera)CD20· Non-Hodgkin’s lymphoma 非霍奇金淋巴瘤 · Chronic lymphocytic leukemia 慢性淋巴細胞白血病 · Rheumatoid arthritis 類風濕性關節炎 · Granulomatosis with polyangiitis 伴隨小管炎的肉芽腫病
Romidepsin (Istodax)HDAC· Cutaneous T-cell lymphoma 皮膚T細胞淋巴瘤 · Peripheral T-cell lymphoma 外周T細胞淋巴瘤
Ruxolitinib (Jakafi)JAK1/2· Myelofibrosis 骨髓纖維化
Siltuximab (Sylvant)IL-6· Multicentric Castleman’s disease 多心性Castleman病
Sipuleucel-T (Provenge)
· Prostate cancer 前列腺癌
Sonidegib (Odomzo)Smoothened· Basal cell carcinoma 基底細胞癌
Sorafenib (Nexavar)VEGFR, PDGFR, KIT, RAF· Hepatocellular carcinoma 肝細胞癌 · Renal cell carcinoma 腎細胞癌 · Thyroid carcinoma 甲狀腺癌
Temsirolimus (Torisel)mTOR· Renal cell carcinoma 腎細胞癌
Tocilizumab (Actemra)IL-6R· Rheumatoid arthritis 類風濕性關節炎 · Juvenile idiopathic arthritis 青少年多發性關節炎
Tofacitinib (Xeljanz)JAK3· Rheumatoid arthritis 類風濕性關節炎
Tositumomab (Bexxar)CD20· Non-Hodgkin’s lymphoma 非霍奇金淋巴瘤
Trametinib (Mekinist)MEK· Melanoma 黑色素瘤 (with BRAF V600 mutation)
Trastuzumab (Herceptin)HER2 (ERBB2/neu)· Breast cancer 乳腺癌(HER2+) · Gastric cancer 胃癌 (HER2+)
Vandetanib (Caprelsa)EGFR (HER1/ERBB1), RET, VEGFR2· Medullary thyroid cancer 甲狀腺髓樣癌
Vemurafenib (Zelboraf)BRAF· Melanoma 黑色素瘤(with BRAF V600 mutation)
Venetoclax (Venclexta)BCL2· Chronic lymphocytic leukemia 慢性淋巴細胞白血病 (with 17p deletion)
Vismodegib (Erivedge)PTCH, Smoothened· Basal cell carcinoma 基底細胞癌
Vorinostat (Zolinza)HDAC· Cutaneous T-cell lymphoma 皮膚T細胞淋巴瘤
Ziv-aflibercept (Zaltrap)PIGF, VEGFA/B· Colorectal cancer 大腸癌

Alt text



閱讀數:2842
关于电子游戏作文600字