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View the Table of Contents for the May 2007 issue of Molecular Cancer Therapeutics
Page 1478
In this issue, Molecular Cancer Therapeutics launches a new feature–Spotlight on Clinical Response—whose objective is the rapid publication of breaking discoveries regarding target- or mechanism-based clinical responses in cancer. The first in this series is a report from Senzer et al. on the first treatment of a hereditary cancer syndrome targeted to the underlying genetic defect responsible for the disease. Their results demonstrated important relationships between treatment response, radiographic findings and molecular markers of p53 tumor suppression that will be valuable in guiding future application of p53 therapy for both familial and non-familial neoplasms with p53 abnormalities.
Page 1492
Human melanoma xenografts respond differently to the regional chemotherapy agents. Yoshimoto et al. utilized five different human melanomas in a xenograft model of extremity melanoma to evaluate the variability of tumor response to regionally administered melphalan (LPAM) or temozolomide (TMZ) and to determine if various components of pertinent drug resistance pathways for LPAM and TMZ could be predictive of tumor response. This study demonstrated that single molecular markers may be useful in predicting the utility of temozolomide based regional therapy for advanced extremity melanoma tumors. The limited ability of single molecular markers to predict response to chemotherapies like LPAM which are detoxified through more complex pathways was also shown.
Page 1509
A rational stepwise screening of thio-BPU derivatives in models of pancreatic cancer identified SG410 as an agent with potential for further development in pancreatic cancer. SG410 has shown at least comparable efficacy with docetaxel in direct comparisons and superior historical activity to other agents approved for pancreatic cancer such as erlotinib, based on our previous data. Additionally, Jimeno et al. have found evidence suggesting that MAPT levels may help in identifying patients more likely to benefit from the drug, which would represent a step forward in the individualization of cancer therapy.
Page 1620
Levels of vascular endothelial growth factor (VEGF) are regulated in part through activation of the PI3K/Akt pathway. Using pharmacological inhibitors, Kurmasheva et al. have examined the relative contributions of Akt and mTOR signaling to VEGF production in neuroblastoma (NB) and rhabdomyosarcoma (RMS) cells growing under normoxic (21% O2) or hypoxic (1% O2) conditions. Combining A-443654 with rapamycin had variable effect on cell proliferation; however, the combination essentially blocked hypoxia-driven increases in VEGF in all cell lines examined, suggesting that dual blockade at different levels in the PI3K-initiated signaling pathway may be a reasonable strategy for preventing VEGF production in cancer cells derived from pediatric solid tumors.