Lorus announces down regulation of GTI-2040 molecular target in breast cancer clinical study
Publication shows rapid reduction in target gene expression in responding tumor tissue
Lorus Therapeutics Inc. announced publication of data demonstrating decreased expression of the molecular target for its antisense drug, GTI-2040, in a Phase II breast cancer clinical trial. The article titled "Analysis of ribonucleotide reductase M2 mRNA levels in patient samples after GTI-2040 antisense drug treatment', to be published in the May issue of oncology Reports (Volume 15, Issue 5, Pages 1299-1304), presents a case study from a National Cancer Institute (NCI) sponsored Phase II clinical trial of GTI-2040 in combination with capecitabine in metastatic breast cancer. The publication describes the development of a rapid and practical method to measure ribonucleotide reductase R2 (also known as M2), a malignant determinant that is the molecular target of GTI-2040 therapy. The trial is sponsored by the cancer therapy Evaluation Program of the US NCI under a clinical trials Agreement between Lorus and the NCI.
In the case presented, a rapid and dramatic reduction in expression of the gene for the R2 component of ribonucleotide reductase was demonstrated in tumor biopsy tissue following treatment with GTI-2040 in combination with capecitabine. An approximately 25-fold decrease in R2 was seen as early as one day after the start of GTI-2040 treatment. This finding, in conjunction with an observed clinical response of six months duration, was paralleled by an observed reduction of the R2 target in circulating white blood cells (WBCs). This decrease suggests a potential utility of WBCs as a "surrogate" tissue for measuring this malignant determinant, and may also be useful for evaluating the activity of GTI-2040 in down regulating target gene expression in patients for whom tumor biopsy is not possible.
Evaluation of additional patient biopsies is continuing in this ongoing study. The authors noted that the findings suggest the method presented has potential for assessing target down regulation by GTI-2040 in a clinical setting.
Other news from the department research and development
