April 15 Cancer Research Highlights

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Selected Articles from the April 15, 2007 Issue

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 Cancer Research is published. Click on the article title to view the complete article.

View the Table of Contents for the April 15 issue of Cancer Research.

Functional Diffusion Mapping Detects Efficacy of Prostate Cancer Therapy in Bone

Due to the high incidence of bone involvement in hormone refractory prostate cancer (PCa), assessment of treatment response in PCa metastasized to the bone remains a major clinical need. Lee et al. investigated the feasibility of using the functional diffusion map (fDM) as an imaging biomarker for assessing early treatment response in a preclinical model of metastatic PCa. Regions of significantly increased diffusion values were detected early using fDM in docetaxel-treated versus untreated metastatic prostate bone tumors, indicating loss of tumor cell viability. Validation of fDM results was accomplished by histological analysis of excised tissue. Results from this study demonstrate the capability of fDM as a biomarker for detection of bone cancer treatment efficacy, which warrants clinical evaluation.

Novel Mutations Profiled in Carcinomas Using the Consensus Coding Sequence Set

Somatic mutations are the hallmark of cancer cells, and recently a systematic genome-wide search for genes mutated in colon and breast cancer has been accomplished. Using this set of genes, Balakrishnan et al. explored the mutational profile of cancer genes in glioblastoma, melanoma, and pancreatic carcinoma. Novel mutations were found in EPHA3, MLL3, TECTA, FBXW7 and OBSCN, suggesting their involvement in the development of these highly malignant tumors. The findings support the concept that cancer genes and their mutational profile are tumor-specific and provide new opportunities for individualized molecular diagnosis and therapeutics.

The Cytochrome P450 Oxidoreductase Locus Alters Breast Cancer Risk in African Americans

Variation in the cytochrome P450 oxidoreductase gene (POR), a key regulator of type II cytochrome P450 enzymes, may affect exposure to endogenous steroid hormones and breast cancer risk. Haiman et al. sequenced the POR locus and tested the candidate polymorphisms G5G and A503V for association with breast cancer risk among women in the Multiethnic Cohort Study. The authors provide statistical evidence that common genetic variation at the POR locus alters breast cancer risk among African Americans. These findings provide strong support for genetic studies in non-Caucasian populations, as not all risk alleles for common diseases will be uncovered by studies limited to European Americans.

Hedgehog Pathway Inhibitor Eradicates Cxcr6-Induced Medulloblastoma

Medulloblastomas caused by mutations in the hedgehog (Hh) pathway are eradicated by the Smoothened inhibitor, HhAntag. Other medulloblastomas exhibit gene expression profiles characteristic of Hh signaling but they do not carry mutations in known Hh pathway genes. To determine the efficacy of HhAntag in these tumors, Sasai et al. investigated medulloblastomas arising in Cxcr6-null mice. Mutation of Cxcr6 caused suppression of Patched-1 expression thereby increasing Smoothened activity. Transplanted tumors were eliminated by treatment with HhAntag. These findings extend the potential range of tumors that are sensitive to Smoothened inhibitors and they suggest an indirect effect of Cxcr6 on Hh activity.

The Role of Tumor-Stromal Interactions in Aromatase Function

There have been controversies regarding both the regulation and the intratumoral localization of aromatase in human breast carcinoma tissues. Miki et al. examined these issues and detected aromatase mRNA and protein in both stromal and parenchymal cells in breast carcinoma tissues. In tumor-stroma coculture experiments, aromatase mRNA and enzyme activity in MCF-7 cells were up-regulated in the presence of patient-derived intratumoral stromal cells. The discovery of a tumor-stroma regulatory relationship for aromatase provides new insight into and may aid in achieving better clinical response to aromatase inhibitors in breast cancer patients.