Radiotherapy-assisted tumor selective metronomic oral chemotherapy

Seung Woo Chung, Seho Kweon, Beom Suk Lee, Gui Chul Kim, Foyez Mahmud, Hanul Lee, Young Seok Cho, Jeong Uk Choi, Ok Cheol Jeon, Ji Won Kim, Seong Who Kim, In-San Kim, Sang Yoon Kim, Youngro Byun

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Chemotherapy have commonly been used in maximum tolerated dose to completely eradicate the cancer. However, such treatments often failed due to the complex and dynamic nature of cancer. Therefore, it has been suggested that cancer should be treated as a chronic disease, controlling its growth by providing continuous therapeutic pressure for long-term. Such an approach, however, requires a therapy that is non-toxic and orally available with sufficient potency. Herein, we propose a radiotherapy-assisted orally available metronomic apoptosis-targeted chemotherapy, which delivers doxorubicin continuously to the irradiated tumor with high selectivity while causing minimal toxicities to the normal tissues. DEVD-S-DOX/DCK complex is the anticancer prodrug for our strategy that could selectively release doxorubicin in the irradiated tumor tissue with sufficient oral bioavailability. The prodrug was completely inactive by itself, but displayed potent anticancer activity when coupled with radiotherapy. Consequently, the daily oral administration of DEVD-S-DOX/DCK in combination with the low-dose radiotherapy effectively suppressed the growth of tumor in vivo with no significant systemic toxicities despite that the accumulated dose of doxorubicin exceeded 150 mg/kg. Therefore, the our novel therapy using DEVD-S-DOX/DCK complex is considered as an outstanding treatment option for treating cancer for long-term attributed to its oral availability and low-toxicity profile as well as the potent anticancer effect.

Original languageEnglish
Pages (from-to)1912-1920
Number of pages9
JournalInternational Journal of Cancer
Volume141
Issue number9
DOIs
Publication statusPublished - 2017 Nov 1

Keywords

  • drug delivery system
  • metronomic therapy
  • oral chemotherapy
  • radiation-induced apoptosis-targeted chemotherapy
  • targeted therapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Chung, S. W., Kweon, S., Lee, B. S., Kim, G. C., Mahmud, F., Lee, H., Cho, Y. S., Choi, J. U., Jeon, O. C., Kim, J. W., Kim, S. W., Kim, I-S., Kim, S. Y., & Byun, Y. (2017). Radiotherapy-assisted tumor selective metronomic oral chemotherapy. International Journal of Cancer, 141(9), 1912-1920. https://doi.org/10.1002/ijc.30842