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Case Rep Oncol. 2014 Jan 24;7(1):79-85. doi: 10.1159/000358382. eCollection 2014.

Two Case Reports of Resensitization to Previous Chemotherapy with the Novel Hypoxia-Activated Hypomethylating Anticancer Agent RRx-001 in Metastatic Colorectal Cancer Patients.

Author information

  • 1Moores Cancer Center, UCSD, La Jolla, Calif., USA.
  • 2Imaging Endpoints, Scottsdale, Ariz., USA.
  • 3RadioRx, Inc., Mountain View, Calif., USA.
  • 4Stanford University Medical Center, Stanford, Calif., USA.

Abstract

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.

KEYWORDS:

Epigenetic resensitization; Hypoxia activation; Oxidation

PMID:
24575021
[PubMed]
PMCID:
PMC3934615
Free PMC Article
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