期刊
CASE REPORTS IN ONCOLOGY
卷 7, 期 1, 页码 79-85出版社
KARGER
DOI: 10.1159/000358382
关键词
Epigenetic resensitization; Oxidation; Hypoxia activation
类别
资金
- NATIONAL CANCER INSTITUTE [P30CA023100] Funding Source: NIH RePORTER
- NCI NIH HHS [P30 CA023100] Funding Source: Medline
The development of chemoresistance is a persistent problem during the treatment of cancer. Although reversion or modification of acquired chemoresistance has been previously observed, no systematic exploration has been undertaken. Here, we report a case study of 2 male patients, 62 and 66 years old, both with histologically proven, radiologically progressing, extensively pretreated, metastatic and refractory (>= 2 conventional regimens and drug therapy) colorectal adenocarcinoma that was previously treated with FOLFIRI. The patients were resensitized to FOLFIRI after exposure to RRx-001 in the context of a phase-1 study. RRx-001 is a novel, hypomethylating and free-radical-inducing anticancer agent that activates nitrite reduction to NO under hypoxia and has an impact on epigenetic pathways. The repression of DNA methyltransferase 1 by RRx-001 may lead to demethylation and reexpression of silenced tumor suppressor genes, leading to resensitization. These examples provide insight into a nascent strategy to improve the prognosis in heavily pretreated cancer patients and suggest routes for further exploration. (C) 2014 S. Karger AG, Basel
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