Many melanomas contain an activating mutation in BRAF: a substitution of glutamic acid for valine at amino acid 600 (the V600E mutation). The authors conducted a two-phase study to describe the activity of a new agent, PLX4032, that inhibits mutated BRAF. A total of 26 of 32 patients (81%) who received 960 mg of PLX4032 orally, twice daily, had a partial or complete response lasting for at least 19 months. Side effects included rash, arthralgia, fatigue, and keratoacanthoma.

In autosomal dominant polycystic kidney disease (ADPKD), aberrant activation of the mammalian target of rapamycin (mTOR) pathway is associated with progressive kidney enlargement. Sirolimus (rapamycin) suppresses mTOR signaling and was studied in this 18-month open-label, randomized, controlled trial involving adults with ADPKD and early chronic kidney disease. Sirolimus at a daily target dose of 2 mg did not halt polycystic kidney growth.

In this 2-year, double-blind trial, patients with ADPKD were randomly assigned to receive either placebo or the mTOR inhibitor everolimus, since the mTOR pathway is important in cyst growth. Although everolimus slowed the increase in kidney volume, as assessed by means of magnetic resonance imaging, it did not slow the progression of renal impairment.