August 1 Clinical Cancer Research Highlights

Selected Articles from the August 1, 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 August 1 issue of Clinical Cancer Research.

VHL Gene Status in Kidney Cancer

Nickerson et al.

Page 4726

Mutation of the von Hippel-Lindau (VHL) gene is thought to be a common, early event in the development of kidney cancer. In this study, Nickerson and colleagues comprehensively evaluated 205 histologically confirmed cases of clear cell renal cancer for VHL mutations and promoter methylation. They found that 91% of cases (a higher percentage than has been previously reported) had VHL inactivation. Further, they found that VHL inactivation through mutation (82.4%) and inactivation through epigenetic mechanisms (8.3%) are mutually exclusive events. These findings provide a more detailed picture of the relationship between somatic mutations and methylation of VHL in clear cell renal tumors.

Identification of Papillary Thyroid Carcinoma-Associated Genes

Oler et al.

Page 4735

Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy. Mutations of effectors along the MAPK pathway are central to malignant transformation, with the BRAF V600E substitution being the most common genetic event. Using SAGE, Oler and colleagues identified genes over-expressed in PTC. Further expression and mutational analysis demonstrated that CST6 (a secreted inhibitor of lysosomal cysteine proteases) and CXCL14 (a newly identified CXC chemokine) levels were positively correlated with the presence of BRAF mutations and with lymph node metastases. These findings suggest that CST6 and CXCL14 play a role in the pathogenesis and progression of PTC and may be downstream targets of BRAF.

Predicting 5FU Therapy Outcome with K-Ras Mutations

Etienne-Grimaldi et al.

Page 4830

The combination of anti-EGFR monoclonal antibodies with 5FU-based therapy is a promising treatment for colorectal cancers. Although K-Ras mutations can be used to predict resistance to anti-EGFR antibodies, it is unclear whether K-Ras mutation status influences 5FU efficacy. Etienne-Grimaldi and colleagues investigated the influence of K-Ras mutations on treatment outcome in 93 stage IV colorectal cancer patients receiving 5FU therapy exclusively. K-Ras mutation status did not influence response rate (44.4% in tumors with K-Ras mutations vs. 32.1% in wild-type tumors) or specific survival. These results suggest that the predictive value of K-Ras mutations in treatments combining anti-EGFR with 5FU should be exclusively linked to the anti-EGFR agent.

Monitoring Photodynamic Therapy Response with PSA

Patel et al.

Page 4869

Photodynamic therapy (PDT) is in clinical trials for the treatment of locally recurrent prostate cancer. Because biochemical response provides one means of monitoring prostate cancer treatment, Patel and colleagues examined PDT-induced changes in prostate serum antigen (PSA) concentration. PDT treatment induced a rapid increase in PSA levels within one day, especially at high doses. High PDT doses also led to a longer delay (when compared with low PDT doses) before PSA rose irreversibly to levels equal to or greater than pre-treatment baseline. These data suggest that PSA response should be considered further for use as an early indicator of PDT outcome.

August 1 Clinical Cancer Research Highlights

Selected Articles from the August 1, 2008 Issue

VHL Gene Status in Kidney Cancer

Identification of Papillary Thyroid Carcinoma-Associated Genes

Predicting 5FU Therapy Outcome with K-Ras Mutations

Monitoring Photodynamic Therapy Response with PSA

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