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Radiotherapy‐assisted tumor selective metronomic oral chemotherapy
Author(s) -
Chung Seung Woo,
Kweon Seho,
Lee Beom Suk,
Kim Gui Chul,
Mahmud Foyez,
Lee Hanul,
Cho Young Seok,
Choi Jeong Uk,
Jeon OkCheol,
Kim Ji Won,
Kim Seong Who,
Kim InSan,
Kim Sang Yoon,
Byun Youngro
Publication year - 2017
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.30842
Subject(s) - prodrug , radiation therapy , chemotherapy , doxorubicin , pharmacology , medicine , cancer , bioavailability , in vivo , toxicity , oral administration , cancer research , oncology , biology , microbiology and biotechnology
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.