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View the Table of Contents for the January 1 issue of Clinical Cancer Research.
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Tubulysins are a novel tubulin-targeted class of natural compounds that are highly active in multidrug-resistant cells, but have no therapeutic window due to high toxicity. Schluep and colleagues synthesized a nanoparticle prodrug of tubulysin A, which is designed to release the drug upon endocytosis by cancer cells. Compared to the small molecule analog, tubulysin nanoparticles displayed a 100-fold increase in maximum tolerated dose and significantly increased antitumor activity in animal models of human cancer. These results suggest that macromolecular prodrugs may facilitate the clinical development of this class of compounds.
Zhang et al. Page 238 Optical imaging technology has the potential to help develop models of metastasis and evaluate the anti-metastatic potential of drugs. Here, Zhang and colleagues applied bioluminescence imaging (BLI) technology to characterize the MDA-MB-435-HAL-Luc subrenal capsule (SRC) and mammary fat pad (MFP) mouse tumor models. Compared to the MDA-MB-435-HAL-Luc MFP model, the SRC model exhibited more efficient, spontaneous metastasis, which significantly affected mouse survival time. BLI allowed quantitative assessment of the anti-tumor and anti-metastatic efficacy of anti-neoplastic agents in both tumor models. These results show that by using an optimized BLI technique, clinically relevant disease models can be developed for evaluating drug effects.
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