PDF Version for Printing
The articles referenced in this Highlights section will be available online in HTML and PDF formats to all interested users at no charge until the next issue of Molecular Cancer Therapeutics is published. Click on the article title to view the complete article.
View the Table of Contents for the February 2007 issue of Molecular Cancer Therapeutics
Lyu et al. Page 460
B lymphocyte stimulator (BLyS) is crucial for B-cell survival and the biological effects of BLyS are mediated by three cell-surface receptors designated BAFF-R, TACI, and BCMA. Increased expression of BLyS and its receptors has been identified in numerous B-cell malignancies. Lyu et al. generated a fusion toxin designated rGel/BLyS for receptor- mediated delivery of the rGel toxin to neoplastic B-cells and characterized its activity against various B-cell tumor lines. Their results suggest that BLyS has the potential to serve as an excellent targeting ligand for the specific delivery of cytotoxic molecules to neoplastic B cells expressing the BLyS receptors and that the rGel/BLyS fusion toxin may be an excellent candidate for the treatment of B-cell malignancies, especially MCL and DLBCL.
Ghajar et al. Page 552
Though attempts to develop any viable chemotherapeutic approaches to combat metastatic cancers have largely failed, potential genetic targets to halt metastatic progression continue to be identified. As drugs are developed to address these targets, there is a need for high-throughput systems that accurately reproduce in vivo microenvironments to gauge their efficacy. Accordingly, Ghajar et al. developed a three-dimensional in vitro culture system representative of the environment present upon secondary metastasis to quantitatively measure tumor cell invasion in this setting three-dimensionally. The authors propose this reported novel, quantitative system as a useful tool to assess the effects of pharmacologic and/or microenvironmental influences on tumor cell invasion at a metastatic site.
Page 570
Sheffer et al. discovered halofuginone as an inhibitor of collagen type I synthesis and previously described its efficacy in prevention and treatment of fibrosis in various pre-clinical models of which excess of collagen is the hallmark of the disease. In this study, the authors demonstrated in prostate cancer and Wilms’ tumor xenograft models that low doses of halofuginone can create synergies with low doses of the respective chemotherapy, reducing tumor progression and reaching the same efficacy as high chemotherapy doses. Halofuginone—already approved for clinical trials—represents a novel targeted therapeutic strategy for combination therapy that would potentially decrease treatment burden.
Page 655
In order to identify a new class of inhibitors that could suppress the growth of chronic myelogenous leukemia (CML) cells and prevent the evolution of cells which are resistant to imatinib, Lerma et al. screened two low complexity libraries of compounds based on planar and linear scaffolds. These libraries were screened using a cell-based assay for molecules that suppress p210Bcr-Abl dependent cell growth. The application of this method resulted in the isolation of two new classes of drugs both of which inhibited imatinib resistant cells in the low micromolar range. Some of these drugs were potent inhibitors not only of Abl tyrosine kinase but also of the Src, Lyn and Fyn tyrosine kinases.