Recent Publications by VICC Researchers

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 work published in peer-reviewed journals by Cancer Center investigators in 2014-2015:

Study in East Asians identifies genes tied to colon cancer risk

Genetic factors identified to date explain only a small fraction of colorectal cancer (CRC), and most studies of hereditary risk have been conducted among people of European descent. Wei Zheng, M.D., Ph.D., and colleagues published results from a genome-wide association study of CRC among East Asians in May 2014 in Nature Genetics. The investigators identified six novel genetic loci that are associated with an increased risk of colorectal cancer among East Asians and suggestive evidence for three additional genetic loci. Two of the genetic loci are linked to the genes TCF7L2 and TGFB1 that have established roles in the development of colorectal tumors. Four others are located in or near genes involved in cell signaling, growth, differentiation, motility and metastasis.

Potential therapy for postpartum breast cancer investigated

Nearly 25 percent of all breast cancers among premenopausal women occur within two to five years following a pregnancy. A study led by Rebecca Cook, Ph.D., and published Nov. 3, 2014, in the Journal of Clinical Investigation helps explain the cellular activity that leads to breast tumor metastasis among women who have recently given birth. After milk production has ended, there is a cascade of cell death and remodeling, with immune suppressive factors driven by a molecule in microphages called MerTK Using a mouse model, Cook and her colleagues found that immune suppression in the postpartum breast triggered by MerTK mistakenly protects tumors, increasing their ability to spread. Treating mice harboring postpartum tumors with an investigational drug labeled BMS-777607, designed to inhibit MerTK, showed decreased clean-up of dying breast cells in the postpartum breast, decreased immune suppression and decreased metastasis.

Study finds accuracy of lung cancer imaging varies by region

A new analysis of published studies found that FDG-PET technology is less accurate in diagnosing lung cancer versus benign disease in regions where infections like histoplasmosis or tuberculosis are common. Histoplasmosis and other fungal diseases are linked to fungi that are often concentrated in bird droppings and are found in soils. The study was led by Stephen Deppen, Ph.D., and Eric Grogan, M.D., MPH, and appeared in the Sept. 24, 2014, issue of the Journal of the American Medical Association. To estimate FDG-PET diagnostic accuracy, the authors reviewed lung cancer abstracts published in a 14-year period and included 70 studies in the meta-analysis. The studies included 8,511 nodules, 60 percent of which were malignant. The authors suggest that the use of FDG-PET to diagnose lung cancer be limited to non-endemic regions unless an institution has substantial and proven expertise in FDG-PET interpretation.

Gene mutation linked to breast cancer therapy resistance

A group of Vanderbilt-led investigators has identified a new gene mutation that may explain why some breast cancer patients do not respond to antiestrogen therapy. The study was published online Nov. 17, 2014, in the Journal of Clinical Investigation and led by Luis Schwarz, M.D., Emily Fox, Ph.D., and Carlos Arteaga, M.D. The investigators profiled ER+ breast tumors from four patients who were treated with the aromatase inhibitor letrozole prior to their mastectomies. These tumors did not respond to the letrozole as measured by markers of proliferation in the mastectomy specimens. The investigators performed deep sequencing on the tumors and identified a novel mutation (D189Y) in a gene of the Src family of kinases called LYN. The investigators also identified other LYN mutations in breast tumors in the Cancer Genome Atlas. Like D189Y, these mutations increase the activity of the LYN protein.

Lung cancer study reveals new drug combination targets

A Vanderbilt lung cancer patient’s exceptional response to different types of therapies spurred research that suggests lung cancer patients with specific gene alterations may benefit from combination therapy that targets two different cancer pathways. The study, led by Christine Lovly, M.D., Ph.D., was published online Aug. 31, 2014, in Nature Medicine. The work was based on an intriguing clinical observation of a female patient with advanced lung cancer who had an unexpected response to a monoclonal antibody that targets the insulin-like growth factor receptor (IGF-1R). Remarkably, the patient remained on the IGF-1R therapy for 17 months and found the patient’s tumor was positive for an ALK gene fusion. The patient was enrolled in another clinical trial testing crizotinib, a drug that targets ALK rearrangements, and her cancer stopped progressing for several more months. The researchers tested the two types of drugs and found that the combination therapy enhanced the ability to slow down the growth of ALK+ lung cancer cells, and found similar results in cell lines from ALK+ lymphoma.

More breast cancer patients opting for mastectomy

Far more breast cancer patients are choosing to undergo mastectomy, including removal of both breasts, instead of choosing breast conservation surgery even when they have early stage disease that is confined to one breast. The rates of increase were steepest among women with lymph node-negative and in situ (contained) disease. The study, led by Kristy Kummerow, M.D., and Mary Hooks, M.D., MBA, was published online in the Nov. 19, 2014, edition of JAMA Surgery. Using the National Cancer Data Base, the investigators studied records of more than 1.2 million adult women treated at centers accredited by the American Cancer Society and the American College of Surgeons Commission on Cancer from Jan. 1, 1998, to Dec. 31, 2011.