Journal Watch
November 22, 2017
New target for colorectal cancer
In a study published March 6 in the journal Oncogene, Dana Hardbower, Ph.D., Keith Wilson, M.D., and colleagues demonstrated that epidermal growth factor receptor (EGFR) signaling in macrophages is associated with increased colitis-associated colon cancer development. While inflammatory bowel disease and colitis can increase the risk of colon cancer, the mechanisms behind this connection are poorly understood. The study showed that in models of colitis-associated cancer, EGFR was highly activated in macrophages. When researchers deleted the EGFR gene in myeloid cells, they were able to reduce colitis and additionally decrease tumor burden in mice.
Investigators match novel cancer mutations with potential therapies
A study led by first author Ariella Hanker, Ph.D., published March 8 in Cancer Discovery, solved a mystery about why a targeted therapy stops working in a small group of breast cancer patients. The researchers identified a novel HER2 gene mutation that develops in the tumors and then found a different cancer drug that appears to treat the newly identified mutation. After identifying this secondary mutation, the VICC investigators tested therapies and found that afatinib, a drug approved for lung cancer appears to be active.
Study identifies protein’s role in chemotherapy resistance
A protein discovered by Vanderbilt scientists may lead to a new way to prevent resistance and improve outcomes for patients whose cancers have mutations in the tumor suppressor gene BRCA2. In a paper published Aug. 3 in Molecular Cell, David Cortez, Ph.D., and colleagues describe how DNA-binding protein, RADX, regulates the activity of another enzyme, which is involved in DNA repair with the BRCA2 protein, in a way that promotes genome stability and modulates drug stability.
Blood type linked to cancer survival
Despite treatment advances with ovarian cancer, overall five-year survival after diagnosis remains low at 45 percent. Two small studies have previously reported shorter survival rates among ovarian cancer cases with blood type A. In a much larger study of 694 patients, the largest such study conducted to date, Alicia Beeghly-Fadiel, MPH, Ph.D., and colleagues found just the opposite. They reported May 8 in PLOS ONE that cases with type A blood were associated with significantly longer ovarian cancer survival.
Pancreatic cancer development
Pancreatic ductal carcinoma is one of the most lethal types of cancer with new therapeutic options needed. Sergey Novitskiy, M.D., Ph.D., and colleagues investigated the immune response during the development of aggressive pancreatic ductal carcinoma in an animal model. They found elevated levels of G-CSF (granulocyte-colony stimulating factor) in the pancreatic epithelium. Inhibiting G-CSF with a blocking antibody in combination with the chemotherapy drug gemcitabine reduced tumor size, decreased the number of immunosuppressive cells and increased the number of infiltrating T cells more effectively than gemcitabine alone. The findings reported Aug. 25 in Cancer Immunology Research suggest that anti-G-CSF treatments may increase the efficacy of conventional interventions with this cancer.
STINGing combination for cancer
Cyclic dinucleotides (CDNs) are intracellular messengers produced in bacteria that can bind to and activate an immune-mediated signaling cascade called STING in mammalian cells. CDNs have shown antitumor activity in melanoma and breast tumors. Reporting in Head & Neck March 21 Young J. Kim, M.D., Ph.D., and colleagues at Johns Hopkins University School of Medicine tested the ability of CDNs to limit tumor growth in a mouse model of head and neck cancer. The researchers used a well-known immunotherapy. That was combined with direct injection of CDNs into the tumors. The novel immunotherapy combination induced “remarkable” regression of established tumors.
Fatty acids and adenoma risk
Dietary intake of polyunsaturated fatty acids (PUFAs) has been associated with risk of colorectal cancer, with increased risk with omega-6 PUFAs that are found predominantly in meat and decreased risk with omega-3 PUFAs that are found predominantly in fish oils. Most studies, however, have relied on questionnaires to assess consumption. Harvey Murff, M.D., MPH, and colleagues took a different approach by studying a blood-based biomarker of PUFA intake in patients who participated in the Tennessee Colorectal Polyp Study, a large colonoscopy-based case-control study. They reported June 29 in the British Journal of Nutrition that higher levels of arachidonic acid (an omega-6 PUFA) were associated with an increased risk of colorectal adenomas. Higher levels of two omega-3 PUFAs (DPA and EPA) were associated with reduced risk. DPA was associated with reduced adenomas, and EPA was associated with reduced advanced adenomas.
Acid reflux cancer link
Esophageal adenocarcinoma is an increasingly common cancer that silently affects the esophagus. What causes it is not well known, but gastroesophageal reflux disease (GERD), characterized by chronic heartburn/acid reflux, is the strongest known risk factor. In a study published Aug. 30 in Scientific Reports, Alexander Zaika, Ph.D., and coworkers show that DNA damage to the esophageal cells caused by acidic bile reflux activate enzymes called NADPH oxidases in the mitochondria to release highly reactive-oxygen species (ROS). Inhibition of ROS induced by reflux may be a useful strategy for preventing DNA damage and decreasing the risk for tumor formation caused by GERD, they concluded.