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View the Table of Contents for the November 15 issue of Clinical Cancer Research.
Dabrosin Page 8036
Angiogenesis may be involved in sex steroid–dependent breast cancer development. Vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2) induce angiogenesis. Posttranslational cleavage of sequestered matrix proteins is involved in the regulation of bioactive proteins in vivo. Dabrosin used microdialysis to sample extracellular VEGF and FGF-2 in normal human breast tissue in situ in pre- and postmenopausal women. Breast tissue VEGF was found to correlate significantly with estradiol, but not progesterone, whereas FGF-2 exhibited no correlation with either sex steroid. Estrogen induction of free extracellular VEGF may be one mechanism involved in sex steroid–dependent breast carcinogenesis.
Yip et al. Page 8131
In this issue, Yip et al. demonstrate the benefit of combining Bcl-2 antisense oligonucleotide (ASO) with ionizing radiation (RT) as a successful therapeutic strategy in treating nasopharyngeal cancer in xenograft models. In particular, when Bcl-2 ASO and RT were readministered, such treated mice survived 80 days beyond that of control mice. Detailed bio-distribution studies were also conducted, demonstrating the apparent colocalization of the ASO molecule with the tumor vasculature, which differs in different tumors, which could also influence tumor response. This study establishes the possibility that combining RT with Bcl-2 ASO is an effective therapeutic strategy for human malignancies.
Kelloff et al. Page 7967
In this Review, collaborators from the NCI, FDA, and academia describe the scientific basis of oncology imaging probes and presents examples of state-of-the art molecular imaging probes and their high promise as oncologic drug development tools. The current regulatory opportunities for new and existing probe development and testing are also reviewed, with a focus on recent FDA guidance to facilitate early clinical development of promising probes. This effort is in concert with the FDA Critical Path Initiative, which has called for the development of tools to increase the speed, efficiency, and cost-effectiveness of drug development for cancer and other diseases.
Cutcliffe et al. Page 7986
Clear cell sarcomas of the kidney (CCSK) are the second most common pediatric renal tumor. The molecular and cellular pathobiology of these tumors has remained elusive, and there are no positive diagnostic markers. Using microarray analysis followed by protein verification, Cutcliffe et al. present novel findings that neural markers are upregulated in CCSK, and that the sonic hedgehog and the AKT pathways are activated. Potential therapeutic targets are also identified. This work suggests mechanisms for proliferation in CCSK and identifies a potential link between neuroectodermal tumors and CCSK.
Hayashida et al. Page 8042
Establishment of a reliable method of predicting the efficacy of chemotherapy and radiotherapy is necessary to provide the most suitable treatment for each cancer patient. Hayashida et al. investigated whether proteomic profiling of serum samples of esophageal cancer patients are capable of being used to predict the efficacy of preoperative chemoradiotherapy. A prediction model of the proteomic pattern was built from 15 pathologically diagnosed responders and 12 nonresponders by machine learning algorithms. They report that this model correctly diagnosed chemoradiosensitivity in 93.3% (14 of 15) of the separate cases in a blinded manner.