Given the abundance of new research, it can be challenging to stay current on the latest advancements and findings. Oncology Times is here to help with summaries of the newest studies to ensure you are up-to-date on the latest innovations in oncology practice.
Geographic inequalities in progress against lung cancer among women in the United States, 1990-2015
Lung cancer death rates among women in most of the U.S. have declined substantially in recent years, however, a recent study found that progress among women in a region covering central Appalachia and southern parts of the Midwest and in northern parts of the Midwest has lagged (Cancer Epidemiol Biomarkers Prev 2018; doi:10.1158/1055-9965.EPI-17-0934). Data showed that, from 1990 to 1999 and 2006 to 2015, lung cancer death rates among women rose by 13 percent in a hot spot encompassing 669 counties in 21 states in central Appalachia and southern parts of the Midwest. Throughout the same period in another hot spot that included 81 counties in four states in the northern Midwest, lung cancer death rates among women rose by 7 percent. Conversely, in the remainder of the contiguous U.S., lung cancer death rates among women fell by 6 percent. Additionally, the research team compared lung cancer death rates among women in each hot spot with those among women in the remainder of the country. In 1990, the death rate for the largest hot spot was 4 percent lower than the death rate for non-hot spot regions, but in 2015, it was 28 percent higher, investigators reported. For the second hot spot, the death rate was 18 percent lower than the non-hot spot death rate in 1990 but equivalent to the non-hot spot death rate in 2015. Researchers used data on the number of lung cancer deaths among women from the NCI's SEER Program database to calculate age-standardized lung cancer death rates for each county in the contiguous U.S. from 1990 to 1999 and 2006 to 2015. “Targeted tobacco control programs could reduce the excess burden of lung cancer among women living in hot spot counties and prevent widening geographic inequity,” investigators concluded.
Multifaceted impact of microRNA 493-5p on genome-stabilizing pathways induces platinum and PARP inhibitor resistance in BRCA2-mutated carcinomas
Researchers have identified a piece of genetic code in certain ovarian tumors that allows them to resist treatment with platinum chemotherapy and PARP inhibitor drugs (Cell Reps 2018; https://doi.org/10.1016/j.celrep.2018.03.038). The microRNA alters several molecular pathways in the cells of ovarian tumors harboring a BRCA2 mutation that restores the cancer cells' ability to repair damage caused by drug treatments, according to the study authors. Data showed that the resistance mechanism caused by a specific microRNA, miR-493-5p, occurred only in BRCA2-mutant ovarian cancers, and not cancers containing a BRCA1 mutation. Investigators found that women with ovarian cancer who had mutated BRCA2 genes, as well as high activity of miR-493-5p in their cancer cells, had much worse survival following platinum chemotherapy than those whose cells had low activity of the microRNA. Researchers sequenced microRNAs extracted from 38 primary and recurrent ovarian tumors, and included some that were sensitive to platinum drugs and others that were resistant. These tumors, along with a larger dataset from The Cancer Genome Atlas, were studied. “Our study highlights a previously unrecognized role for miR-493-5p as a potential biomarker of responsiveness to platinum and PARP inhibitors, as well as a target for reversing platinum and PARP inhibitors resistance in BRCA2-mutated ovarian carcinomas,” researchers noted.
ADOPTIVE T-CELL THERAPY
Gut microbiota modulates adoptive cell therapy via CD8α dendritic cells and IL-12
New research suggests that the composition of bacteria in the gastrointestinal tract may hold clues to help predict which cancer patients are most likely to benefit from personalized cellular therapies (JCI Insight 2018; doi:10.1172/jci.insight.94952). Researchers found that the effectiveness of adoptive T-cell therapy (ACT) in mice with cancer is significantly affected by differences in the natural makeup of gut bacteria and treatment with antibiotics. Additionally, they reported that the utilization of fecal transplants affected the efficacy of ACT between different strains of lab rodents. Analysis demonstrated that when ACT was performed on genetically identical animals obtained from different vendors (Jackson Laboratory or Harlan Laboratories), which carry different microbiota, impact of the therapy was not identical. Animals obtained from Harlan showed a much stronger anti-tumor effect compared to animals from Jackson, according to investigators. Additionally, the study showed that depletion of gram-positive bacteria within the gut using vancomycin also increased the efficacy of the therapy, improving the anti-tumor response and overall remission rate in less-responsive mice. The beneficial responses were associated with an increase in systemic dendritic cells, which in turn increased the expression of interleukin 12, that sustained expansion and anti-tumor effects of transferred T cells. Researchers transplanted fecal microbiota from Jackson mice to Harlan mice to define the relationship between gut bacteria and the efficacy of ACT. They determined that Harlan mice transplanted with Jackson microbiota copied the anti-tumor response and tumor growth of Jackson mice. “The present study underscores the importance of the gut bacteria to ACT immunomodulation via IL-12-mediated effects on systemic expansion and tumor invasion of the adoptively transferred T cells,” study authors wrote.
Effects of a group-mediated exercise and dietary intervention in the treatment of prostate cancer patients undergoing androgen deprivation therapy: results from the IDEA-P trial
Men undergoing androgen deprivation therapy (ADT) for prostate cancer face a number of potential side effects, including loss of strength and muscle mass, as well as an increased risk of other health problems such as heart disease and diabetes. New research suggests diet and moderate exercise may help combat the side effects of hormone therapy (Ann Behav Med 2018; doi:10.1093/abm/kax002). Half the men enrolled in the study participated in a 12-week personalized program that included group exercise and nutrition counseling. The other half received some basic education related to their cancer diagnosis and the opportunity for exercise education at the end of the study. Before the study, all the men were sedentary, exercising less than an hour a week in the previous 6 months. Researchers evaluated patients at the beginning of the study, 2 months after the program, and then 3 months after the program. They found the exercise and diet group saw gains in mobility and muscle strength and decreases in fat mass 3 months after the intervention, while those three measures moved in the opposite direction for the other cohort. Men in the intervention group, on average, lost about 4.4 pounds, 4 pounds of which was fat. Their body fat percentage dropped by more than 2 percent. Meanwhile, the control group gained a third of a pound and almost 2 pounds of fat mass on average. Their body fat percentage increased by 1.8 percent, investigators reported. “Collectively, these results suggest that the exercise and dietary intervention was a safe and well-tolerated intervention for prostate cancer patients on ADT,” researchers concluded. “The utility of implementing this approach in the treatment of prostate cancer patients on ADT should be evaluated in future large-scale efficacy trials.”
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