April 15 Clinical Cancer Research Highlights

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Selected Articles from the April 15, 2006 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 April 15 issue of Clinical Cancer Research.

Melanoma Antigen Falters as Immunotherapy Target

Tyrosinase is a melanoma antigen capable of eliciting diverse cellular and serological immune responses. Lindsey et al. conducted two clinical trials evaluating the impact of heterologous prime/boost vaccination with recombinant poxvirus/tyrosinase vaccines, with or without systemic interleukin 2 (IL-2), in patients with advanced metastatic melanoma. In vitro evidence of immunization was observed in up to 25% of patients, and antigen loss tumor variants were observed. Vaccines alone were ineffective in mediating tumor regression, however, and in combination with IL-2 did not enhance clinical benefit. Proteins such as tyrosinase, which are not important for maintaining the malignant cell phenotype, may provide suboptimal targets for immunotherapy.

Hepatocytes Weather TRAIL Treatment, Solo or Combined with Select Therapeutics

Compatibility with hepatocyte survival is an important prerequisite for clinical applicability of TRAIL/Apo2L as a new cancer drug, but has been controversially debated in the past. Ganten et al. comprehensively examined the effect of four recombinant forms of TRAIL on primary hepatocytes from 50 human livers. Three out of four TRAIL forms do not kill primary human hepatocytes. Intriguingly, with the exception of cisplatin, combinations of TRAIL with chemotherapeutics known to sensitize tumor cells for TRAIL do not kill primary hepatocytes. Consequently, TRAIL may be broadly used in tumor therapy either alone or combined with many, but not all, chemotherapeutics.

Deoxycytidine Kinase Labeling Stratifies Patients for Gemcitabine Response

Gemcitabine is often administered as a first-line therapy for patients newly diagnosed with pancreatic cancer. To determine those patients who may most benefit from gemcitabine, Sebastiani et al. used immunohistochemical labeling of deoxycytidine kinase (dCK), the rate-limiting step in enzymatic activation of gemcitabine, in a series of pancreatic cancer tissues from patients subsequently treated with gemcitabine. Importantly, dCK labeling correlated with both overall and disease-free survival following gemcitabine treatment. This approach shows promise as a clinical decision tool to better stratify patients with pancreatic cancer into therapeutic regimens that may include gemcitabine.

Bcl-2 Independently Predicts Breast Cancer Outcome

The validation of prognostic markers in breast cancer is essential to improve clinical outcome prediction. Using tissue microarrays, Callagy et al. profiled 13 protein biomarkers in over 900 breast cancers and eight markers showed significant association with survival. On multivariate analysis, only Bcl-2 remained independent of the Nottingham Prognostic Index (NPI), which is derived from tumor size, tumor grade, and lymph node status. In an independent series of over 1,900 patients, Bcl-2 was validated as a prognostic marker independent of the NPI. These data are strongly supportive of Bcl-2 being an independent predictor of breast cancer outcome.