Phase ib of sorafenib in combination with everolimus in patients with advanced solid tumors, selected on the basis of molecular targets.

Background: Molecular alterations of the PI3K and Ras pathways often occur in human cancer. In this trial, the pharmacokinetics, toxicity, and activity of two drugs inhibiting these pathways-everolimus and sorafenib-were investigated.

Methods: Thirteen patients with progressing solid tumors were treated with everolimus and sorafenib, according to a 3+3 scheme.

Block of CFTR-dependent chloride currents by inhibitors of multidrug resistance-associated proteins.

The cystic fibrosis transmembrane conductance regulator (CFTR) is a membrane protein that belongs to the same family as multidrug resistance-associated proteins whose main function is to expel xenobiotics and physiological organic anions from the cell interior. Despite the overall structural similarity with these membrane proteins, CFTR is not an active transporter but is instead a Cl- channel. We have tested the ability of known inhibitors of multidrug resistance-associated proteins to affect CFTR Cl- currents.

Antihypertensive 1,4-dihydropyridines as correctors of the cystic fibrosis transmembrane conductance regulator channel gating defect caused by cystic fibrosis mutations.

Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel gene. CF mutations like deltaF508 cause both a mistrafficking of the protein and a gating defect. Other mutations, like G551D, cause only a gating defect.