Publication Highlights: July & August 2022
Dominika Kowalczyk and her Glasgow colleagues continued their work into the ubiquitination and degradation pathway of the tumour suppressor p53. In their recent article in Life Science Alliance, they described an intramolecular interaction between MDM2 and the tumour suppressor p14ARF that partially blocks the E2 binding site of MDM2 and therefore inhibits the MDM2-p53 signalling axis.
Together with fellow scientists at the University of Edinburgh, Kristina Kirschner's lab developed a new mathematical framework – built on longitudinal DNA sequencing data – to estimate the impact of mutations in clonal haematopoiesis genes on the growth potential of cells. In addition to identifying gene-specific effects on proliferation, they also suggested a time point for clinical follow up of patients who carry genetic mutations with significant fitness advantages. Read more in Longitudinal dynamics of clonal hematopoiesis identifies gene-specific fitness effects
In a joint effort with the CRUK West of Scotland Clinical Trials Unit, Hing Leung and others reported on the findings of the SPECTRE trial, which investigated the effects of statins in combination with androgen deprivation therapy on castration resistant prostate cancer (CPRC). Although there was evidence that CPRC was stabilised, the treatment effects were below the required criteria to move the trial on to stage 2. The authors suggested that future studies should focus on the long-term effects of statin therapy together with standard-of-care treatment.
Mahnoor Mahmood and Payam Gammage, in collaboration with scientists at the Memorial Sloan Kettering Center in New York, reviewed the current understanding of cancer-associated mutations in mitochondrial DNA in Trends in Cancer. Although these mutations are abundant, recent technological advances now allow researchers to unveil the, so far unknown, functional significance of mtDNA variation.