Anti-tubulin drugs conjugated to anti-ErbB antibodies selectively radiosensitize.
Anti-tubulin drugs conjugated to anti-ErbB antibodies selectively radiosensitize.
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DOI：
10.1038/ncomms13019
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发表时间：
2016-10-04
影响因子：
16.6
通讯作者：
Advani, Sunil J.
中科院分区：
文献类型：
--
作者：
Adams, Stephen R.;Yang, Howard C.;Savariar, Elamprakash N.;Aguilera, Joe;Crisp, Jessica L.;Jones, Karra A.;Whitney, Michael A.;Lippman, Scott M.;Cohen, Ezra E. W.;Tsien, Roger Y.;Advani, Sunil J.
Tumour resistance to radiotherapy remains a barrier to improving cancer patient outcomes. To overcome radioresistance, certain drugs have been found to sensitize cells to ionizing radiation (IR). In theory, more potent radiosensitizing drugs should increase tumour kill and improve patient outcomes. In practice, clinical utility of potent radiosensitizing drugs is curtailed by off-target side effects. Here we report potent anti-tubulin drugs conjugated to anti-ErbB antibodies selectively radiosensitize to tumours based on surface receptor expression. While two classes of potent anti-tubulins, auristatins and maytansinoids, indiscriminately radiosensitize tumour cells, conjugating these potent anti-tubulins to anti-ErbB antibodies restrict their radiosensitizing capacity. Of translational significance, we report that a clinically used maytansinoid ADC, ado-trastuzumab emtansine (T-DM1), with IR prolongs tumour control in target expressing HER2+ tumours but not target negative tumours. In contrast to ErbB signal inhibition, our findings establish an alternative therapeutic paradigm for ErbB-based radiosensitization using antibodies to restrict radiosensitizer delivery. Drugs that sensitize tumour cells to ionizing radiation are prized because they can overcome resistance to radiotherapy. Here, the authors show that anti-tubulin drugs conjugated to cetuximab or trastuzumab can radiosensitize EGFR- or HER2-expressing tumors by increasing DNA damage and cell death due to ionizing radiation.
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影响因子：
51.1
作者：
Bradley, Jeffrey D.;Paulus, Rebecca;Komaki, Ritsuko;Masters, Gregory;Blumenschein, George;Schild, Steven;Bogart, Jeffrey;Hu, Chen;Forster, Kenneth;Magliocco, Anthony;Kavadi, Vivek;Garces, Yolanda I.;Narayan, Samir;Iyengar, Puneeth;Robinson, Cliff;Wynn, Raymond B.;Koprowski, Christopher;Meng, Joanne;Beitler, Jonathan;Gaur, Rakesh;Curran, Walter, Jr.;Choy, Hak
通讯作者：
Choy, Hak
影响因子：
46.9
作者：
Lyon, Robert P.;Setter, Jocelyn R.;Senter, Peter D.
通讯作者：
Senter, Peter D.
影响因子：
3.9
作者：
Creedon, Helen;Byron, Adam;Brunton, Valerie G.
通讯作者：
Brunton, Valerie G.
影响因子：
11.5
作者：
Hamblett, KJ;Senter, PD;Francisco, JA
通讯作者：
Francisco, JA
从放射肿瘤学临床试验中汲取的经验教训。
DOI：
10.1158/1078-0432.ccr-13-1116
发表时间：
2013-11-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Liu FF;workshop participants;Okunieff P;Bernhard EJ;Stone HB;Yoo S;Coleman CN;Vikram B;Brown M;Buatti J;Guha C
通讯作者：
Guha C