Primary and acquired resistance to EGFR-targeted therapies in colorectal cancer: impact on future treatment strategies.
Primary and acquired resistance to EGFR-targeted therapies in colorectal cancer: impact on future treatment strategies.
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DOI：
10.1007/s00109-014-1161-2
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发表时间：
2014-07
影响因子：
4.7
通讯作者：
Trusolino, Livio
中科院分区：
文献类型：
--
作者：
Leto, Simonetta M.;Trusolino, Livio
关键词：
只有大约10%的遗传性化疗难治性转移性结直肠癌患者在接受抗表皮生长因子受体（EGFR）抗体西妥昔单抗或帕尼单抗（“原发性”或“从头”耐药）治疗时经历肿瘤消退。此外，几乎所有肿瘤最初有反应的患者都不可避免地变得难治（“继发性”或“获得性”耐药）。已经描述了越来越多的抗EGFR抗体的原发性和获得性耐药的预测因子，现在很明显，大多数潜在的机制显著重叠。通过尝试从许多特殊的细节中推断出一个统一的观点，在这里，我们讨论了治疗耐药性的分子基础，总结了旨在改善患者选择的研究工作，并提出了目前正在开发的替代治疗策略，以增加反应和对抗复发。
Only approximately 10 % of genetically unselected patients with chemorefractory metastatic colorectal cancer experience tumor regression when treated with the anti-epidermal growth factor receptor (EGFR) antibodies cetuximab or panitumumab (“primary” or “de novo” resistance). Moreover, nearly all patients whose tumors initially respond inevitably become refractory (“secondary” or “acquired” resistance). An ever-increasing number of predictors of both primary and acquired resistance to anti-EGFR antibodies have been described, and it is now evident that most of the underlying mechanisms significantly overlap. By trying to extrapolate a unifying perspective out of many idiosyncratic details, here, we discuss the molecular underpinnings of therapeutic resistance, summarize research efforts aimed to improve patient selection, and present alternative therapeutic strategies that are now under development to increase response and combat relapse.
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影响因子：
28.2
作者：
Bardelli A;Corso S;Bertotti A;Hobor S;Valtorta E;Siravegna G;Sartore-Bianchi A;Scala E;Cassingena A;Zecchin D;Apicella M;Migliardi G;Galimi F;Lauricella C;Zanon C;Perera T;Veronese S;Corti G;Amatu A;Gambacorta M;Diaz LA Jr;Sausen M;Velculescu VE;Comoglio P;Trusolino L;Di Nicolantonio F;Giordano S;Siena S
通讯作者：
Siena S
影响因子：
50.3
作者：
Agus, DB;Akita, RW;Sliwkowski, MX
通讯作者：
Sliwkowski, MX
影响因子：
8.4
作者：
Bokemeyer, Carsten;Van Cutsem, Eric;Koehne, Claus-Henning
通讯作者：
Koehne, Claus-Henning
影响因子：
2.6
作者：
Connolly, K.;Brungs, D.;Epstein, R. J.
通讯作者：
Epstein, R. J.
影响因子：
8
作者：
Brantley, DM;Cheng, N;Chen, J
通讯作者：
Chen, J