American Association for Cancer Research

August 15 Clinical Cancer Research Highlights

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Selected Articles from the August 15, 2005 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 Clinical Cancer Research is published. Click on the article title to view the complete article.

View the Table of Contents for the August 15 issue of Clinical Cancer Research.


Imaging Detects Small Molecule Inhibition of Early Tumor Rim Vascular Permeability

Marzola et al.
Page 5827

CCR 08-15-05 Marzola 5827SU11248, a small-molecule tyrosine kinase inhibitor with direct antitumor and antiangiogenic activity, is currently in advanced clinical trials for various kinds of cancer. By using noninvasive dynamic contrast enhanced-MRI in an experimental model of colon carcinoma, Marzola et al. demonstrated in vivo antiangiogenic activity of SU11248 at a very early time point (24 hours after a single administration of 45 mg/Kg). SU11248 antiangiogenic activity was detected by using either a macromolecular or a low molecular weight contrast agent (Magnevist, Shering, Germany). Because Magnevist is largely used in the clinic, this study is highly relevant for the design of clinical trials based on new paradigms.

 


Proteomic Analysis of Follicular Lymphomas Reveals Prognostic Markers

Gulmann et al.
Page 5847

Though generally incurable, follicular lymphoma (FL) has a varied clinical course and identification of new prognostic markers is crucial. To explore the usefulness of proteomic technology to address this need, Gulmann et al. used reverse phase protein microarrays to analyze apoptotic pathways in tissue samples of FL and benign follicular hyperplasia. Bcl-2/Bak and Bcl-2/Bax ratios were found to be elevated in FL and high ratios were associated with significantly earlier death among FL patients. These findings highlight the promise of proteomic analysis for identifying prognostic cancer biomarkers and suggesting possible candidates for targeted therapy.


Epstein-Barr Virus DNA Level Predicts Treatment Outcomes for Nasopharyngeal Carcinoma Patients

Le et al.
Page 5700

Because most nasopharyngeal carcinoma (NPC) patients harbor the Epstein-Barr virus (EBV) genome in their tumors, several PCR assays have been developed to detect circulating EBV DNA levels. Le et al. compared the performance of three different PCR assays (Pol-1, Lmp2, and BamHI-W) in quantifying plasma EBV DNA in NPC patients. The Pol-1 assay was more accurate than others in predicting EBV DNA concentrations in cell lines, however, each of the assays yielded similar EBV levels in plasma samples. As detected by the Pol-1 assay, post treatment EBV level was an independent predictor for treatment outcomes in 59 endemic and nonendemic NPC patients.

 


Molecular Classification Indicates Breast Cancer Response to Therapy

Rouzier et al.
Page 5678

Novel molecular classification of breast cancer based on gene expression profiles was proposed recently and it was shown that the different molecular subtypes have different prognoses. Rouzier et al. examined whether breast cancers differentially classified by molecular profile also show distinct sensitivity to preoperative chemotherapy. They report that basal-like and erbB2+ subtypes are more sensitive to oral preoperative chemotherapy with paclitaxel and doxorubicin than the luminal and normal-like breast cancers. The genes associated with response were different between the basal-like and erbB2+ subgroups. This suggests that the mechanisms of chemotherapy sensitivity may vary across the subtypes and that distinct predictive signatures might be developed for different molecular subtypes.


 

Gefitinib Extends Survival for NSCLC Patients with EGFR Kinase-Activating Mutations

Taron et al.
Page 5878

CCR 08-15-05 Taron 5878Activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) are associated with response to gefitinib in 94% of chemorefractory non–small cell lung cancer patients. Taron et al. determined that median survival was not reached in patients with EGFR mutations. In addition, patients with EGFR mutations had an increased number of CA repeats in intron 1 of EGFR, increased EGFR gene copy numbers, and higher levels of EGFR mRNA. Survival was longer for patients harboring both EGFR mutations and high levels of EGFR or caveolin-1 mRNA levels.