American Association for Cancer Research

February 15 Clinical Cancer Research Highlights

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Selected Articles from the February 15, 2008 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 February 15 issue of Clinical Cancer Research.


Identifying Druggable Breast Cancer Targets

Ocaña and Pandiella

Page 961

The identification of druggable oncogenic alterations is a major goal of cancer research and drug development. In their review, Ocaña and Pandiella give a global overview of the molecular alterations in breast cancer that are susceptible to being targeted with drugs. They describe in detail genomic and proteomic alterations that are known to occur in breast cancer and show how this knowledge is translated to develop new cancer drugs. They also discuss the use of preclinical models to test new drugs and describe the safety and efficacy of drugs that have been used in the clinic. 


ID2 Regulates Invasion in Hepatocellular Carcinoma

Tsunedomi et al.

Page 1025

The helix-loop-helix transcription factor ID2 is down-regulated in hepatocellular carcinoma (HCC) with invasion of the portal vein. To explore the molecular and biological function of ID2 in HCC, Tsunedomi and colleagues measured its expression level in 92 HCC samples and performed in vitro migration experiments. They found that ID2 mRNA levels are an independent risk factor for early intrahepatic recurrence due to metastasis. In vitro studies showed that ID2 negatively regulates cell migration and invasion, and that this regulation may involve a reduction in vascular endothelial growth factor (VEGF) levels. These results show that ID2 is a potential diagnostic marker and therapeutic target in HCC.


A PI3K Isoform Regulates Neuroblastoma Growth

Boller et al.

Page 1172

The phosphoinositide 3-kinase (PI3K)/Akt pathway is frequently activated in human cancer and plays a crucial role in neuroblastoma biology. To date, the role of individual PI3K isoforms in this pediatric cancer remain elusive. Boller and colleagues investigated the expression pattern and functions of class IA PI3K isoforms in tumor samples and cell lines. Our results show for the first time that p110δ is overexpressed in a subset of neuroblastoma samples and plays a crucial role in the growth and survival of neuroblastoma cells. Therefore, the PI3K isoform p110δ may represent a novel molecular target for neuroblastoma. 
 

Merchant et al.

Page 1182

Merchant et al.TNF-α converting enzyme (TACE) has been implicated in the cleavage of the epidermal growth factor receptor (EGFR) ligands transforming growth factor-α (TGF-α) and amphiregulin at the cell surface. Here, Merchant and colleagues show in a polarizing colorectal cancer (CRC) cell line that TACE, TGF-α, amphiregulin, and EGFR all localize to the basolateral cell surface, and they describe the spatial compartmentalization of these components as the EGFR axis. They found that TACE is overexpressed in primary and metastatic CRC tumors compared with normal colonic mucosa and that its expression is inversely correlated to that of TGF-α and amphiregulin. Furthermore, pharmacologic blockade using a monoclonal antibody against EGFR, a tyrosine kinase inhibitor, and a selective TACE inhibitor resulted in cooperative growth inhibition and increased apoptosis, implicating TACE as a promising target for EGFR axis inhibition in CRC. 


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