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- W2078008046 abstract "Combination of radiotherapy and chemotherapy has emerged as the dominant form of cancer adjuvant treatment in recent years. Several drugs, such as cisplatin, 5-fluorouracil (5-FU) and gemcitabine have been shown to increase tumor sensitivity to radiotherapy. Clofarabine, a newly approved drug for the treatment of pediatric leukemia, is a second-generation nucleoside analogue that may also have the radiosensitizing potential. The active form of clofarabine, clofarabine 5′-triphosphate, a potent inhibitor of DNA polymerase -α, -ε, and ribonucleotide reductase, can block DNA synthesis and possibly inhibit DNA repair. Therefore, we hypothesized that clofarabine could work synergistically with radiotherapy to increase tumor cell responses to ionizing radiation (IR). We report here that, low doses of clofarabine can prolong the existence of radiation-induced γ-H2AX nuclear focus formation, while high doses of clofarabine can induce DNA double strand breaks, suggesting that clofarabine can interfere with DNA damage pathways. A significant decrease in clonogenic survival was observed in irradiated cells treated with clofarabine, demonstrating a strong synergistic effect between clofarabine and radiotherapy. Comparing the radiosensitization potential of clofarabine, gemcitabine and 5-FU, clofarabine displayed a higher radiosensitizing effect than the other two. In addition, clofarabine-induced radiosensitization was also established in vivo using a colorectal cancer model, DLD-1, in athymic nude mice. When combined with fractionated radiotherapy, a moderate dose of clofarabine led to a significant increase in tumor growth inhibition. Collectively, these results demonstrate clofarabine as a powerful radiosensitizer both in vitro and in vivo by inhibiting the repair of DNA damage, culminating in decreases in tumor survival and can be readily translated into clinical studies." @default.
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- W2078008046 date "2007-11-01" @default.
- W2078008046 modified "2023-09-27" @default.
- W2078008046 title "The In Vitro and In Vivo Radiosensitization Effect of Cloforabine" @default.
- W2078008046 doi "https://doi.org/10.1016/j.ijrobp.2007.07.1910" @default.
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