The paradox of cancer genes in non-malignant conditions: implications for precision medicine

AbstractNext-generation sequencing has enabled patient selection for targeted drugs, some of which have shown remarkable efficacy in cancers that have the cognate molecular signatures. Intriguingly, rapidly emerging data indicate that altered genes representing oncogenic drivers can also be found in sporadic non-malignant conditions, some of which have negligible and/or low potential for transformation to cancer. For instance, activatingKRAS mutations are discerned in endometriosis and in brain arteriovenous malformations, inactivatingTP53 tumor suppressor mutations in rheumatoid arthritis synovium, andAKT,MAPK, andAMPK pathway gene alterations in the brains of Alzheimer ’s disease patients. Furthermore, these types of alterations may also characterize hereditary conditions that result in diverse disabilities and that are associated with a range of lifetime susceptibility to the development of cancer, varying from near universal to no elevated risk. Very recently, the repurposing of targeted cancer drugs for non-malignant conditions that are associated with these genomic alterations has yielded therapeutic successes. For instance, the phenotypic manifestations of CLOVES syndrome, which is characterized by tissue overgrowth and complex vascular anomalies that result from the activation ofPIK3CA mutations, can be ameliorated by the PIK3CA inhibitor alpelisib, which was developed and approved for breast cancer. In this review, we discuss the profound implications of findin...
Source: Genome Medicine - Category: Genetics & Stem Cells Source Type: research

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Source: New Zealand Medical Journal - Category: General Medicine Tags: N Z Med J Source Type: research
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Source: New Zealand Medical Journal - Category: General Medicine Tags: N Z Med J Source Type: research
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Source: Expert Opinion on Pharmacotherapy - Category: Drugs & Pharmacology Tags: Expert Opin Pharmacother Source Type: research
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Source: Expert Opinion on Pharmacotherapy - Category: Drugs & Pharmacology Tags: Expert Opin Pharmacother Source Type: research
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Source: Brain, Behavior, and Immunity - Category: Neurology Source Type: research
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