Anti-tubulin drugs conjugated to anti-ErbB antibodies selectively radiosensitize.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Adams, SR; Yang, HC; Savariar, EN; Aguilera, J; Crisp, JL; Jones, KA; Whitney, MA; Lippman, SM; Cohen, EEW; Tsien, RY; Advani, SJ

Published Date

  • October 4, 2016

Published In

Volume / Issue

  • 7 /

Start / End Page

  • 13019 -

PubMed ID

  • 27698471

Pubmed Central ID

  • PMC5059467

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/ncomms13019

Language

  • eng

Conference Location

  • England