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. 2018 Nov 26;8:544. doi: 10.3389/fonc.2018.00544

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Copyright © 2018 Tahover, Bar-Shalom, Sapir, Pfeffer, Nemirovsky, Turner, Gips, Ohana, Corn, Wang and Gabizon.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Graphical representation of the proposed mechanism of radio-sensitization by Promitil. The process includes the following steps in sequence. (A) Promitil reaches tumor site via EPR effect, limited prodrug activation and MMC release takes place in tumor initiating the radio-sensitizing effect. (B) Radiation-damaged cells secrete SH compounds that activate the prodrug MLP amplifying the generation of MMC and subsequent radiosensitizing effect by alkylation and formation of DNA adducts. (C) Schematic drawing of the prodrug MLP with the disulfide bridge sensitive to free thiols and leading to the release of MMC. Adapted with permission from Tian et al. (11).