Publication Highlights: April 2021
This month’s publications highlight the collaborative science that the Beatson regularly participates in both in the UK and around the world.
In research published in Nature Metabolism (Respiratory complex and tissue lineage drive recurrent mutations in tumour mtDNA), Payam Gammage, together with colleagues at the Memorial Sloan Kettering Cancer Center in New York, found that mutations in mitochondrial DNA (mtDNA) increased the chances of survival for patients with bowel cancer. The researchers compiled the largest study of tumour samples to date that investigated the mitochondrial genome. Over 20 cancer types were investigated and more than half of the samples showed mutations within mtDNA. Using this information may aid more accurate prognosis and the development of new treatments in the future.
Beatson scientists David Stevenson, Colin Nixon, Douglas Strathdee and Owen Sansom joined a study, led by the CRUK Edinburgh Centre, on treatment resistance in colorectal cancer (CRC) [RAC1B modulates intestinal tumourigenesis via modulation of WNT and EGFR signalling pathways]. As reported in Nature Communications, they frequently detected RAC1B in late stage patient samples and linked its presence to aggressive CRC tumour types. Mechanistically RAC1B is required for the activation of EGFR signalling, and researchers are now translating their in vitro findings into clinical studies of EGFR inhibitors such as cetuximab with anti-RAC1B treatment for enhanced therapeutic success.
In a preprint available on bioRxiv Hing Leung, Arnaud Blomme and colleagues linked the THEM6 protein to drug resistance in advanced prostate cancer (THEM6-mediated lipid remodelling sustains stress resistance in cancer). THEM6 affected the lipid composition of cancer cells, thus altering a cell's stress response, such as that induced by anti-cancer therapy. As the scientists also observed that THEM6 created a 'tumour stimulating' environment in other hormone-dependent cancers, they propose it as a new therapeutic target beyond just prostate cancer.
Together with Karen Blyth, Alexei Vazquez, Dimitris Athineos and Matthias Pietzke, Institute of Cancer scientists investigated the metabolic role of immune-regulated IDO1 that is associated with aggressive pancreatic cancer (Immune-regulated IDO1-dependent tryptophan metabolism is source of one-carbon units for pancreatic cancer and stellate cells). They demonstrated a shift in preference towards tryptophan as a fuel for specialised metabolism that can aid cancer growth. The administration of anti-IOD1 therapy may enhance metabolically-targeted treatment strategies such as serine and glycine restriction but requires further research.