Journal Watch

Vanderbilt-Ingram Cancer Center is committed to conducting innovative, high-impact basic, translational and clinical research with the greatest potential for making a difference for cancer patients, today and in the future. Here’s a sampling of recent work published in peer-reviewed journals by center investigators:

Cancer biomarker boost
Daniel Liebler, Ph.D., Lisa Zimmerman, Ph.D., and colleagues in the National Cancer Institute’s Clinical Proteomic Technology Assessment for Cancer (CPTAC) program have developed a new method for detecting and quantifying cancer-associated proteins in body fluids. The new method combines two existing mass spectrometry-based technologies: multiple reaction monitoring (MRM) coupled with stable isotope dilution mass spectrometry (SID-MS). In the July issue of Nature Biotechnology, they report that this combination of proteomics methods increases accuracy and reproducibility of candidate biomarker verification, ensuring that the best biomarker candidates are carried through to clinical validation. The findings may offer a major boost to the development of biomarkers to aid in early cancer detection and personalized cancer therapy – including the development of blood tests for cancer detection.

Gene signature predicts breast cancer prognosis
Vanderbilt-Ingram researchers have uncovered a gene signature that may help predict clinical outcomes in certain types of breast cancer. In the June issue of the Journal of Clinical Investigation, Harold (Hal) Moses, M.D., and colleagues report that this gene signature – which is associated with the transforming growth factor-beta (TGF-β) signaling pathway – correlates with reduced relapse-free survival in patients with breast cancer, especially in those with estrogen receptor-positive tumors. The results suggest that assessing TGF-β signaling may be a useful aid in determining breast cancer prognosis and in guiding treatment. The work also sheds light on how TGF-β affects tumor growth and progression.

Breast cancer ‘hot spot’
Wei Zheng, M.D., Ph.D., and colleagues have identified a new genetic hot spot for breast cancer on chromosome 6. Reported in the March issue of Nature Genetics, this genetic variation – a single nucleotide polymorphism (SNP) – may explain about 18 percent of breast cancer cases in the general population. Women with one copy of this SNP have about 40 percent increased risk of breast cancer; having two copies of the SNP increases risk about 60 percent. Although the function of the SNP is not clear, it is strongly associated with estrogen receptor (ER)-negative cases of breast cancer, which carry a worse prognosis than ER-positive cases. Zheng hopes to use this SNP and others to build a risk prediction model that could help identify high-risk women for chemoprevention or regular cancer screening to reduce their breast cancer mortality.

Sweet approach to cancer prevention
The main sweet-tasting chemical component of licorice (glycyrrhizic acid) may offer a new approach to preventing colorectal cancer without the adverse side effects of other preventive therapies. In a study published in the April Journal of Clinical Investigation, Raymond Harris, M.D., Ming-Zhi Zhang, M.D., and colleagues show that inhibiting the enzyme 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2) – either by treatment with glycyrrhizic acid or by silencing the 11βHSD2 gene – prevents colorectal cancer progression in mice predisposed to the disease. While this natural chemical is an appealing drug lead in itself, the researchers are working to develop more specific and potent inhibitors of 11βHSD2.

Life and death in the stomach lining
Infection with the gut bacterium Helicobacter pylori increases the risk of gastric cancer, in part by disrupting the delicate balance between cell proliferation and death in the stomach lining. Using gastric cell cultures and mouse models of H. pylori infection, Brent Polk, M.D., and colleagues found that the bacterially induced activation of the epidermal growth factor receptor (EGFR) – a molecule that regulates cell survival – protects gastric epithelial cells from programmed cell death (apoptosis) and that blocking this activation increased H. pylori-induced apoptosis. The findings reported in the April issue of Gastroenterology offer insights into how H. pylori infection might contribute to the development of gastric cancer and support the strategy of targeting EGFR for cancer prevention or treatment.

Lithium shields brain from radiation damage
Cranial irradiation is part of standard therapy for both primary and metastatic brain tumors. However, as with all treatment modalities, radiation often causes long-term side effects. In particular, neurological impairments – including lowered IQ, learning difficulties and memory loss – have been reported, especially in children treated for brain cancers. In the May issue of the Journal of Clinical Investigation, Fen Xia, M.D., Ph.D., and colleagues show that lithium – a drug widely used to treat bipolar mood disorder – promotes DNA repair in healthy cells but not in brain tumor cells. The findings suggest that lithium treatment could offer a way to protect healthy brain tissue from damage that may occur during cranial radiation treatments.

More information about our research at: www.vicc.org/research