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 recent work published in peer-reviewed journals by center investigators:

New melanoma drug shows promise

A personalized approach to treating metastatic melanoma is showing promise, according to a clinical trial reported in the Aug. 26 New England Journal of Medicine. Igor Puzanov, M.D., Jeffrey Sosman, M.D., and colleagues report that treatment with the investigational drug PLX4032 caused significant tumor shrinkage in 81 percent of metastatic melanoma patients with the BRAFV600Emutation. Among 32 patients, two patients had complete responses with no evidence of disease, and 24 patients had tumor shrinkage of at least 30 percent. Progression-free survival among these patients was at least seven months, compared to less than two months in most clinical trials. While the majority of patients showed tumor shrinkage while taking the drug, some tumors eventually progressed. Puzanov and Sosman were also involved in detailing the drug’s development and how it works on a molecular level, findings published Sept. 7 in the journal Nature.

Potential breast cancer drug target identified

Two-thirds of breast cancers depend on the female hormone estrogen for growth. Anti-estrogen drugs can block this growth; however many women eventually develop resistance to anti-estrogen therapies. In the July 1 Journal of Clinical Investigation, Carlos Arteaga, M.D., Todd Miller, Ph.D., and colleagues show that the PI3-kinase (PI3K) signaling pathway may be a promising target for new therapies to overcome this resistance. In breast cancer cell lines, PI3K signaling was required for the cells to become hormone-independent. An investigational inhibitor of PI3K/mTOR slowed or stopped growth in all of the cell lines and triggered cell death in three of the four cell lines used. The findings suggest that patients who relapse on anti-estrogen therapy – and whose tumors exhibit a high degree of PI3K signaling – may benefit from treatments targeting both the estrogen receptor and the PI3K pathways.

Childhood cancer survivors risk stillbirth

Advances in cancer management have led to a sharp increase in the number of childhood cancer survivors who reach adulthood and want to have children. In the Aug. 21 issue of The Lancet, John Boice Jr., Sc.D., Lisa Signorello, Sc.D., and colleagues report that female survivors of childhood cancer – especially those exposed to high doses of pelvic radiation – were up to 12 times more likely to experience a stillbirth or death of their baby than other survivors. For girls treated before puberty, even lower radiation doses (1.0-2.5 Gy) were linked to an increased risk of stillbirth or neonatal death. However, men who had received radiation of the testes showed no increased risk among their children. The findings suggest that pregnancy in women treated with high-dose radiation before puberty should be carefully managed.

Markers help predict breast cancer risk

Asian women have lower incidence of breast cancer than North American and European women, but rates are beginning to spike. In the July 7 Journal of the National Cancer Institute, Wei Zheng, M.D., Ph.D., M.P.H., and colleagues report a risk prediction model that can help identify women at high risk for breast cancer. The researchers devised a “genetic risk score” based on eight genetic variants associated with breast cancer risk among Chinese women. The genetic risk score, along with a patient’s waist-to-hip ratio and a previous diagnosis of benign breast disease, were the top three predictors of breast cancer risk. Since annual screening mammography is difficult to justify given the low incidence of breast cancer in Asian countries, combining genetic and clinical predictors to identify high-risk women for screening might be beneficial in this population.

Remain vigilant for second cancers

While nearly 80 percent of childhood cancer patients are surviving five years or more after diagnosis, they continue to face ongoing health risks, including the development of subsequent cancers. Debra Friedman, M.D., and colleagues report in the July 21 Journal of the National Cancer Institute that the risk of developing subsequent cancers increases with age and that survivors of Hodgkin lymphoma are at the greatest risk. Increased risk was also seen in female survivors, survivors diagnosed at an older age, and survivors treated with radiation. This risk did not decrease with time. The findings demonstrate that childhood cancer survivors continue to be at increased risk of subsequent cancers through the second and third decades of life, and suggest that continued surveillance and medical follow-up for these survivors is essential.

Healthy lifestyle combo for longer life

A combination of healthy lifestyle factors – normal weight, low belly fat, regular physical activity, limited exposure to secondhand cigarette smoke, and higher consumption of fruits and vegetables – may have a major combined impact on mortality among individuals who do not smoke or drink alcohol regularly. Using data from 71,243 non-smoking, non-drinking Chinese women aged 40 to 70 years, Wei Zheng, M.D., Ph.D., M.P.H., and colleagues assigned points for each healthy lifestyle factor to arrive at a healthy lifestyle score. In the journal PLoS Medicine, they report women with a higher healthy lifestyle score (4 or 5 points) had a 43 percent lower risk of mortality from all causes than women with a zero score. Women with higher scores also showed lower mortality from cardiovascular diseases and cancer, specifically.