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This Week in Clinical Cancer Research: Oct 28, 2011


In Clinical Cancer Research, researchers in the US and Europe elucidated the biological role of transcription factor Sp1 in multiple myeloma. Sp1 controls a number of cellular processes, the researchers write. For this study, they investigated functional Sp1 activity in multiple myeloma cell lines, and found that there is high Sp1 activity in the cancer cells and that it is further induced by adhesion to bone marrow stromal cells. "Sp1 knockdown decreases MM cell proliferation and induces apoptosis," the team says. "Sp1-DNA binding inhibition by [small molecule terameprocol] inhibits MM cell growth both in vitro and in vivo, inducing caspase-9–dependent apoptosis and overcoming the protective effects of BMSCs." Sp1 is an important transcription factor in multiple myeloma, they conclude, and can be therapeutically targeted.

Also in Clinical Cancer Research this week, researchers in the US and Singapore say that high expression of the XRCC1 protein in patients with head and neck squamous cell carcinoma is associated with poorer survival. The team evaluated XRCC1 expression in 138 head and neck cancer patients treated with surgery, and found that patients with high expression had poorer median overall survival and poorer progression-free survival than patients with low XRCC1 expression. "This association was primarily due to patients who received chemoradiation," the team says. "In patients treated with nonchemoradiation modalities, there was no survival difference by XRCC1 expression."

Finally in Clinical Cancer Research this week, an international team of researchers reports a mechanism of tamoxifen resistance in breast cancer. Using microarray analysis, the researchers observed that treatment-resistant metastatic breast tumors had elevated levels of the Dicer gene. When they over-expressed Dicer in ERα-positive MCF-7 human breast cancer cells, they saw a concomitant increase in the expression of the breast cancer resistance protein. "In the presence of Tamoxifen, Dicer-overexpressing cells formed resistant colonies in soft agar, and treatment with BCRP inhibitors restored Tamoxifen sensitivity," the authors write. "Dicer-overexpressing breast cancer cells are enriched for cells with enhanced BCRP function. We hypothesize that it is this population which may be involved in the emergence of Tamoxifen-resistant growth. BCRP may be a novel clinical target to restore Tamoxifen sensitivity."

The Scan

Researchers Compare WGS, Exome Sequencing-Based Mendelian Disease Diagnosis

Investigators find a diagnostic edge for whole-genome sequencing, while highlighting the cost advantages and improving diagnostic rate of exome sequencing in EJHG.

Researchers Retrace Key Mutations in Reassorted H1N1 Swine Flu Virus With Avian-Like Features

Mutations in the acidic polymerase-coding gene boost the pathogenicity and transmissibility of Eurasian avian-like H1N1 swine influenza viruses, a PNAS paper finds.

Genome Sequences Reveal Evolutionary History of South America's Canids

An analysis in PNAS of South American canid species' genomes offers a look at their evolutionary history, as well as their relationships and adaptations.

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.