Introduction to the Biochemical Pharmacology special issue on targeted cancer therapy.
Introduction to the Biochemical Pharmacology special issue on targeted cancer therapy.
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关于癌症靶向治疗的生化药理学特刊简介。
DOI：
10.1016/j.bcp.2010.03.003
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发表时间：
2010
影响因子：
5.8
通讯作者：
Smalley,KeiranSM
中科院分区：
文献类型：
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作者：
Smalley,KeiranSM
美国癌症协会（American Cancer Society）（www.癌org）表明，平均每个人有1/2的机会患上癌症，使癌症成为西方社会的第二大死亡原因。生物医学研究现在站在癌症治疗史上一个有趣的十字路口。以前的策略，旨在不分青红皂白地杀死快速分裂的细胞，开始被更有选择性的方法所取代，这些方法专门针对导致肿瘤发生和发展的遗传变化。如果这一领域继续如预期的那样发展，可以预见未来癌症治疗将个性化，允许最大的治疗益处和最小的脱靶效应。目前正在开发的许多新的治疗方法是20世纪80年代发生的“癌基因革命”的直接结果，这导致了恶性转化所必需的基因突变的鉴定。这些突变通常发生在受体酪氨酸激酶（RTK）中，如c-KIT（GIST）、Bcr-ABL（慢性髓性白血病）、表皮生长因子（EGF）受体（结直肠癌、肺癌的一些亚组）以及GTP酶，如KRAS（结肠癌、肺癌）和丝氨酸/苏氨酸激酶BRAF（黑色素瘤、甲状腺癌、结直肠癌）[1-3]。现在，几年后，有证据表明，如果靶向正确的致癌突变，可以实现令人印象深刻的临床反应。c-KIT/Bcr-ABL激酶抑制剂伊马替尼已成为不可切除的胃肠道间质瘤（GIST）和慢性粒细胞白血病（CML）的标准治疗[4]。当在黑色素瘤中靶向突变的BRAF [5]并且在髓母细胞瘤患者中抑制Hedgehog信号传导[6]时，也观察到类似的令人鼓舞的结果。
Statistics from the American Cancer Society (www. cancer. org) indicate that the average person has a 1 in 2 chance of developing cancer making cancer the second leading cause of death in Western Society. Biomedical research now stands at an interesting crossroad in the history of cancer therapy. Previous strategies, aimed at the indiscriminate killing of rapidly dividing cells, are beginning to be replaced by more selective approaches that specifically target the genetic changes responsible for tumor initiation and progression. If this field continues to advance as anticipated, a future can be foreseen where cancer therapies are personalized to the individual patient, allowing for maximal therapeutic benefit with minimal off-target effects.Many of the novel therapeutic approaches currently under development are a direct result of the “oncogene revolution” that occurred in the 1980s, which led to the identification of the genetic mutations necessary for malignant transformation. These mutations typically occur in the receptor tyrosine kinases (RTKs), such as c-KIT (GIST), Bcr-ABL (chronic myeloid leukemia), the epidermal growth factor (EGF) receptor (colorectal carcinoma, some subgroups of lung cancer), as well as GTPases, eg, KRAS (colon carcinoma, lung cancer) and serine/threonine kinases BRAF (melanoma, thyroid cancer, colorectal carcinoma)[1–3]. Now, several years later, there is evidence that impressive clinical responses can be achieved provided the correct oncogenic mutations are targeted. The c-KIT/Bcr-ABL kinase inhibitor imatinib has become the standard of care for unresectable gastrointestinal stromal tumors (GIST) and chronic myeloid leukemia (CML)[4]. Similar encouraging results have also been observed when mutated BRAF is targeted in melanoma [5] and Hedgehog signaling is inhibited in patients with medulloblastoma [6].
影响因子：
158.5
作者：
Druker, BJ;Talpaz, M;Sawyers, CL
通讯作者：
Sawyers, CL
PLX4032 的 I 期研究：V600E BRAF 突变作为人类癌症治疗靶点的概念证明。
DOI：
10.1200/jco.2009.27.15_suppl.9000
发表时间：
2016
期刊：
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
影响因子：
--
作者：
K. Flaherty;I. Puzanov;J. Sosman;K. Kim;A. Ribas;G. McArthur;R. J. Lee;J. Grippo;K. Nolop;P. Chapman
通讯作者：
P. Chapman
DOI：
10.1073/pnas.0405220101
发表时间：
2004-09-07
影响因子：
11.1
作者：
Pao, W;Miller, V;Varmus, H
通讯作者：
Varmus, H