Macias Receives Prostate Cancer Foundation Young Investigator Award and NIH Research Supplement to Promote Diversity in Health-Related Research

August 1, 2014

Everardo Macias_Chi LabDurham, NC —Everardo Macias, PhD, a Research Scientist in the Department of Molecular Genetics and Microbiology working collaboratively in the laboratories of Ashley Chi, PhD and Stephen Freedland, MD, was recently awarded a Prostate Cancer Foundation Young Investigator Award and an NIH Research Supplement to Promote Diversity in Health-Related Research from the National Cancer Institute under the parent grant entitled “Gene expression programs of lactic acidosis in human cancers.” The overarching goals of these awards are to explore survival mechanisms of cancer cells under various tumor micorenvironmental stresses and nutrient deprivation.

According to Macias and others, there is a clear and consistent link between obesity and prostate cancer mortality. Moreover, there is a suggestion that weight loss may reduce the risk of developing high-grade prostate cancer. Likewise, in animal models caloric restriction consistently slows prostate growth in xenograft and transgenic mouse models. However, nutrient deprivation and calorie restriction apparently leads to only a modest tumor response. This suggests there must be either intrinsic or acquired resistance mechanisms that allow tumor cells to continue to survive or even proliferate. To identify these resistance mechanisms, Macias will use an in vivofunctional genomic screen to identify kinases that are essential for survival of prostate cancer cells under nutrient deprived conditions. The goal is to ultimately identify kinases that can be targeted by small molecule inhibitors to enhance the anti-tumoral efficacy of dietary interventions.

In addition, Macias will evaluate the role of a family of ribosomal associated protein kinases that appear to be crucial for cell survival under a range of microenvironmental stresses.  Interestingly, analyses of large-scale cancer genomic data sets suggest that this family of ribosomal kinases is frequently altered across various tumor types and most strikingly altered in prostate cancers. Collectively, these two awards support studies that will reveal the mechanisms of acquired resistance mechanisms by which tumor cells survive and continue to grow under various stress conditions and nutrient deprivation. Such insights may provide actionable targets for the management of prostate cancer and other solid tumors.