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This Week in Clinical Cancer Research: Jan 13, 2012


In Clinical Cancer Research this week, a team led by researchers at the National Cancer Institute says polycomb repressor complex-2 could be a novel target for mesothelioma therapy. Polycomb group proteins mediate stem cell pluripotency, and have been implicated in the pathogenesis of several cancers, the authors write. The researchers examined PcG protein expression in cultured malignant pleural mesotheliomas, mesothelioma specimens, and normal mesothelial cells, finding that the genes EZH2 and EED — which encode components of polycomb repressor complex-2 — were over-expressed in mesothelioma cell lines compared to normal mesothelial tissue. "EZH2 was over-expressed in approximately 85 percent of MPMs compared with normal pleura, correlating with diminished patient survival," the team says. "Pharmacologic inhibition of PRC-2 expression/activity is a novel strategy for mesothelioma therapy."

Also in Clinical Cancer Research this week, another NCI team assesses the efficacy of anti-CD25 recombinant immunotoxin LMB-2 in combination with chemotherapy for the treatment of adult T-cell leukemia. The team grew tumor xenografts expressing human CD25 in mice, and then treated the animals with LMB-2 and chemotherapy alone and in combination. They found evidence to suggest that CD25 interacts with LMB-2 in tumors. "Intratumoral sCD25 levels were in the range 21 to 157 (median 54) ng/mL without treatment and 0.95 to 6.1 (median 2.6) ng/mL one day after gemcitabine administration," the team writes. "CD25+ xenografts that were too large to regress with LMB-2 alone were minimally responsive to gemcitabine alone but completely regressed with the combination."

In a paper published online in advance in Clinical Cancer Research this week, a team of researchers in Japan reports on a novel risk classification system for ovarian cancer, based on a 126-gene expression signature. The team analyzed data from 1,054 ovarian cancer patients, and found that its 126-gene expression signature could help predict overall survival. "Through gene ontology and pathway analyses, we identified a significant reduction in expression of immune-response related genes, especially on the antigen presentation pathway, in high-risk ovarian cancer patients," the authors write. "This risk classification based on the 126-gene expression signature is an accurate predictor of clinical outcome in patients with advanced-stage high-grade serous ovarian cancer and has the potential to develop new therapeutic strategies for high-grade serous ovarian cancer patients."

The Scan

Genetic Testing Approach Explores Origins of Blastocyst Aneuploidy

Investigators in AJHG distinguish between aneuploidy events related to meiotic missegregation in haploid cells and those involving post-zygotic mitotic errors and mosaicism.

Study Looks at Parent Uncertainties After Children's Severe Combined Immunodeficiency Diagnoses

A qualitative study in EJHG looks at personal, practical, scientific, and existential uncertainties in parents as their children go through SCID diagnoses, treatment, and post-treatment stages.

Antimicrobial Resistance Study Highlights Key Protein Domains

By screening diverse versions of an outer membrane porin protein in Vibrio cholerae, researchers in PLOS Genetics flagged protein domain regions influencing antimicrobial resistance.

Latent HIV Found in White Blood Cells of Individuals on Long-Term Treatments

Researchers in Nature Microbiology find HIV genetic material in monocyte white blood cells and in macrophages that differentiated from them in individuals on HIV-suppressive treatment.