Targeting KRAS mutant cancers using a novel inhibitor of PLK1 substrate binding

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Cancer is a genetic disease caused by mutations in key genes that regulate cell-growth and survival. In recent years, new ‘targeted’ therapies that aim to functionally reverse the root genetic causes of cancer have shown success in many cancer types. However Pancreatic tumours, a particularly lethal form of cancer, has not benefited from such advances; primarily due to the difficulty in ‘drugging’ its predominant driver-gene called ‘KRAS’. PhoreMost has developed a strategy that allows us to bypass this direct drugging problem by developing first-in-class inhibitors that bind to a novel site in a separate but well established cancer clinical target (PLK1), which display a previously unappreciated combined 'synthetic lethality' with mutant KRAS. In this grant we be optimising the potency and selectivity of these compounds and then testing them for their efficacy in vivo, which if successful we will partner with a pharmaceutical company for further testing in clinical trials.