Function and expression of p-glycoprotein in blood-tissue barriers; translational studies

This thesis reveals additional insights in the functional behavior of P-glycoprotein in the human blood brain barrier, in P-glycoprotein expression and function in animal models, and in P-glycoprotein expression in the human blood-testis barrier and in testicular tumors. The blood-brain barrier is a major obstacle for drug delivery to the brain. Many anti-cancer, anti-epileptic, or anti-HIV drugs reach, due to the blood-brain barrier function, relatively low brain concentrations, resulting in poor efficacy of these drugs in the brain. For that reason the brain is often considered a sanctuary, harboring unaffected cancer cells during chemotherapy. Increasing drug delivery to the brain may lead to better treatment results, e.g. of brain metastases. One major target to increase drug levels in the brain is the efflux pump P-glycoprotein, which has been demonstrated to efflux many substrates from the brain to the blood.

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