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This Week in Clinical Cancer Research: Feb 18, 2011


In this week's Clinical Cancer Research, researchers in Taiwan say reduced p21WAF1/CIP1 via alteration of p53-DDX3 pathway is associated with poor relapse-free survival in early-stage HPV-associated lung cancer. Using real-time PCR, luciferase assays, immunoprecipitation, and chromatin immunoprecipitation, the researchers determined that three p53 binding sites were required for DDX3 transcription, and that DDX3 deregulation could lead to cell proliferation and the ability to form colonies. The team adds: "The reduction of p21 by the alteration of the p53-DDX3 pathway plays an essential role in early-stage HPV-associated lung tumorigenesis and is correlated with poor [relapse-free survival] of lung cancer patients."

Also in Clinical Cancer Research this week, researchers at the University of Alabama say that exosomes — small membrane-bound particles released from normal, diseased, and neoplastic cells into the blood — can be used to take unneeded endogenous molecules out of cells and transport therapeutic drugs into them. "When exosomes are taken up by specific cells, they may act locally to provide autocrine or paracrine signals or, at a distance, as a newly described nanoparticle-based endocrine system," the researchers write. "In cancer, signals via exosomes affect the immune system by inhibiting the functions of T cells and normal killer cells and by inhibiting the differentiation of precursors to mature antigen-presenting cells." Exosomes could be used clinically in the development of vaccines and in targeting tumors, they add.

An international team of researchers present their findings on KRAS mutation in lung metastasis in patients with curatively resected colorectal cancer. The researchers looked for differences in oncogene mutation profiles between colorectal cancer metastases from different sites and found mutations in four of 19 oncogenes. KRAS mutation prevalence was significantly higher in the lung and brain than in the liver, the team says, and "mutation status was highly concordant between primary cancer and metastasis from the same individual."

And finally in Clinical Cancer Research this week, a team of researchers present their study on the link between androgen receptor expression and breast cancer survival in post-menopausal women. By studying postmenopausal women with stage I to III breast cancer, the researchers found that androgen receptor positivity was associated with significant reduction in mortality. "Determination of AR status may provide additional information on prognosis for postmenopausal women with breast cancer, and provide novel opportunities for targeted therapy," the team writes.

The Scan

Lung Cancer Response to Checkpoint Inhibitors Reflected in Circulating Tumor DNA

In non-small cell lung cancer patients, researchers find in JCO Precision Oncology that survival benefits after immune checkpoint blockade coincide with a dip in ctDNA levels.

Study Reviews Family, Provider Responses to Rapid Whole-Genome Sequencing Follow-up

Investigators identified in the European Journal of Human Genetics variable follow-up practices after rapid whole-genome sequencing.

BMI-Related Variants Show Age-Related Stability in UK Biobank Participants

Researchers followed body mass index variant stability with genomic structural equation modeling and genome-wide association studies of 40- to 72-year olds in PLOS Genetics.

Genome Sequences Reveal Range Mutations in Induced Pluripotent Stem Cells

Researchers in Nature Genetics detect somatic mutation variation across iPSCs generated from blood or skin fibroblast cell sources, along with selection for BCOR gene mutations.