Research ArticleCancer therapy

HIF-independent synthetic lethality between CDK4/6 inhibition and VHL loss across species

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Science Signaling  01 Oct 2019:
Vol. 12, Issue 601, eaay0482
DOI: 10.1126/scisignal.aay0482

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New treatment for kidney cancer

People with von Hippel-Lindau syndrome, caused by loss of the namesake gene VHL, commonly develop cysts in the kidneys and are at an increased risk of developing a type of kidney cancer called clear cell renal cell carcinoma (ccRCC). Currently, drugs that inhibit the hypoxia-inducible transcription factor HIF-2α show some efficacy but only in some patients. Nicholson et al. performed a screen to identify targets that selectively limited the growth of VHL−/− fly cells. Confirmed in human ccRCC cells and patient-derived xenografts in mice, they found that inhibiting the cyclin-dependent kinases CDK4 and CDK6 together impaired tumor growth in VHL−/− ccRCC regardless of HIF-2α dependency. These findings suggest a potential and more broadly applicable therapy for ccRCC patients.

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