American Association for Cancer Research

November 1 Cancer Research Highlights

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Selected Articles from the November 1, 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 November 1 issue of Cancer Research.


Tissue-Engineered Bone Is a Breast Cancer Target

Moreau et al.

Page 10304

The high propensity of breast cancer to metastasize to bone results from contributions on both sides of the tumor-stroma interface. Identifying the components in bone (growth factors, etc.) essential for metastasis is challenging. To investigate bone–breast cancer interactions, Moreau and colleagues created engineered bone by adding human marrow-derived mesenchymal stem cells to silk fiber scaffolds.  Later, metastases were demonstrated to form in engineered bone from human breast cancer cells originating at the orthotopic site in a mouse model. Since engineered bone can be manipulated in controlled fashion, it is now possible to use it to identify bone components essential for metastasis. 
 

Pregnane X Receptor Enhances Chemotherapy in Prostate Cancer

Chen et al.

Page 10361

As a sensor of xenobiotics, pregnane X receptor (PXR) regulates the gene expression of drug metabolizing enzymes and efflux transporters that can have profound effects on the efficacy of chemotherapy. Chen and colleagues found that prostate cancer cells expressed functional PXR which, when activated, rendered tumor cells with increased resistance to Taxol and vinblastine. Ablation of PXR in prostate cancer cells enhanced the efficacy of chemotherapy. Since PXR can be activated by a range of chemotherapeutics and herbal supplements, potential activation of PXR should be taken into consideration when designing combination chemotherapy for prostate cancer.


Mutagenesis Screen Indentifies EGFR Inhibitors

Yu et al.

Page 10417

Yu et al.Secondary EGFR mutations commonly lead to resistance to the EGFR inhibitors erlotinib and gefitinib in patients with non–small cell lung cancer. Irreversible EGFR inhibitors, such as CL-387,785 can overcome resistance and are in clinical development. Yu and colleagues developed a cell-based, in vitro random mutagenesis screen to identify EGFR mutations that confer resistance to CL-387,785 and identified a number of novel resistance mutations. Both an alternative EGFR inhibitor and a Cdk4 inhibitor could overcome such resistance. These results identify novel mutations mediating resistance to irreversible EGFR inhibitors and reveal alternative strategies to overcome or prevent resistance in EGFR-mutant lung cancers.


Mah et al.

Page 10484

Mah et al.Lung cancer remains the most lethal type of human malignancy, with increased incidences occurring especially in women. Mah and coauthors describe novel findings about the prognostic value of aromatase expression in predicting the course of non–small cell lung cancer (NSCLC). This group demonstrated the importance of estrogen and aromatase for promoting tumor progression in a mouse model. They further conducted a population-based study examining aromatase levels in human NSCLC using tissue microarray technology. Lower levels of aromatase were a strong predictor of survival in women older than 65 years with earlier stage cancer. The authors predict that the use of aromatase inhibitors may benefit this patient population.


Lymph Node Microenvironment Alters Sensitivity to Estradiol

Harrell et al.

Page 10582

Estrogen-responsive breast tumors often become refractory to antiestrogens and recur in organs distant from the primary site. To determine if the lymph node (LN) microenvironment alters tumor-cell sensitivity to estradiol, Harrell and colleagues developed a model to assess the hormone responsiveness of xenografted human breast tumors and their matched LN metastases. Laser-capture microdissection plus gene expression profiling confirmed by immunohistochemistry, found that LN metastases were estrogen insensitive compared to the primary tumors. Indeed, some genes were regulated by estradiol in the opposite direction in tumors and matched metastases. This study shows that the LN microenvironment influences expression of therapeutic targets that may alter cancer cell survival, recurrence, or response to treatments.