American Association for Cancer Research

December 1 Clinical Cancer Research Highlights

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Selected Articles from the December 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 Clinical Cancer Research is published. Click on the article title to view the complete article.

View the Table of Contents for the December 1 issue of Clinical Cancer Research.

Validity of Complete Remission Data Questioned

Haessler et al.

Page 7073

Long-term myeloma survival has been reported in the absence of complete remission (CR). Using data from a large tandem transplant trial, Haessler and investigators re-examined the clinical relevance of CR for survival in the context of gene expression profiling data on CD138-purified myeloma cells. The authors observed that, in the context of gene array data, CR status conferred a favorable effect on both event-free and overall survival only among the 13% of patients presenting with a high risk score. These data call into question the validity of CR as a surrogate for prolonged survival in all myeloma patients. 
 

Promoter Hypermethylation Negatively Influences Chemotherapy

Grövdal et al.

Page 7107

Promoter hypermethylation of the genes P15INK4b, E-cadherin, and hypermethylated in cancer 1 genes was examined by Grövdal and colleagues in 60 patients with high-risk myelodysplastic syndromes or acute myeloid leukemia following myelodysplastic syndrome prior to treatment with induction chemotherapy. The authors found that hypermethylation was associated with bone marrow CD34 expression, but not with cytogenetic pattern. Promoter hypermethylation of more than one gene was shown to negatively influence the outcome of chemotherapy; no patient with methylation of all three genes achieved complete remission. The role of promotor methylation status should be further evaluated in prospective clinical trials and may be an important factor in the therapeutic decision-making for these patient groups.

Measles Virus and Radiation Therapy Combine to Treat Glioblastoma Multiforme

Liu et al.

Page 7155

Radiation therapy (RT) represents a key therapeutic modality in the treatment of glioblastoma multiforme, the most common glioma histology; nevertheless, most tumors recur within the radiation field, and median survival is only 12 to 15 months. Liu and colleagues demonstrated that combining RT with the oncolytic measles virus strain MV-CEA resulted in synergistic antitumor activity in vitro and in vivo and significant enhancement of cytotoxicity. MV-CEA is currently in clinical testing in recurrent glioma patients, and these results could have immediate translational implications in glioma treatment. 

Yang et al. The functional responses of ovarian cancer-specific T cells have not been directly investigated in vivo. Yang and colleagues developed a new murine model involving an epitope-tagged version of HER-2/neu to enable tracking of tumor-specific CD8+ T cell responses to ovarian cancer. Adoptively transferred CD8+ OT-I T cells underwent a striking proliferative response and induced complete tumor regression, even in animals with highly advanced disease. By contrast, OT-I cells with impaired IL-2/IL-15 signaling failed to expand significantly or induce tumor regression. Thus, advanced ovarian cancers can support extraordinary CD8+ T cell proliferation and antitumor activity through an IL-2/IL-15-dependent mechanism.

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