Decoding the interplay between genetic and non-genetic drivers of metastasis nature.com - get the latest breaking news, showbiz & celebrity photos, sport news & rumours, viral videos and top stories from nature.com Daily Mail and Mail on Sunday newspapers.
Acquired drug resistance to anticancer targeted therapies remains an unsolved clinical problem. Although many drivers of acquired drug resistance have been identified1–4, the underlying molecular mechanisms shaping tumour evolution during treatment are incompletely understood. Genomic profiling of patient tumours has implicated apolipoprotein B messenger RNA editing catalytic polypeptide-like (APOBEC) cytidine deaminases in tumour evolution; however, their role during therapy and the development of acquired drug resistance is undefined. Here we report that lung cancer targeted therapies commonly used in the clinic can induce cytidine deaminase APOBEC3A (A3A), leading to sustained mutagenesis in drug-tolerant cancer cells persisting during therapy. Therapy-induced A3A promotes the formation of double-strand DNA breaks, increasing genomic instability in drug-tolerant persisters. Deletion of A3A reduces APOBEC mutations and structural variations in persister cells and delays t
Study Reveals How Epstein-Barr Virus May Lead to Cancer nih.gov - get the latest breaking news, showbiz & celebrity photos, sport news & rumours, viral videos and top stories from nih.gov Daily Mail and Mail on Sunday newspapers.
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Researchers at the Francis Crick Institute, as part of an international collaboration of scientists through the Pan-Cancer Analysis of Whole Genomes Consortium, have analysed the whole genomes of tumour samples from over 2,600 patients with different types of cancer. They identified a high prevalence of genetic diversity within individual tumours, which they further characterised. Their findings confirm that, even at late stages of development, tumour evolution is driven by changes that benefit the cancer.
When cancer cells divide, errors occur in the process of copying their DNA. These copying errors mean that different tumours can be made up of cells presenting a wide range of genetic diversity. This variation is a challenge for doctors as a treatment that works for one group of genetically related tumour cells, called a subclone, may not be effective against another. And certain subclones can initiate tumour spread or drug resistance.