Mechanistic pharmacokinetic, -dynamic, and -genetic studies

If the mechanism behind an interaction is known in detail, it should also be possible to avoid severe drug-related toxicities. With this is mind, and in close collaboration with the group of dr Sparreboom (St. Jude, Memphis, USA) we studied cisplatin-related nephrotoxicity.

We found an important role for the organic cation transporter 2 (OCT2) in regulating the uptake of this drug in the proximal tubules. Next, we explored in mice and human if the OCT2 inhibitor was capable to reduce nephrotoxicity without reducing the systemic exposure to cisplatin. We have also performed mechanistic studies for other drugs, like sorafenib (www.trialregister.nl , studynumber NTR4110). (Bins et al, Clin Transl Sci 2017)

In addition, a large multicentre randomized clinical trial (CABARESC) that studied the potential protective effects of budesonide on cabazitaxel related diarrhea in prostate cancer patients. This study was recently presented (ESMO 2016) and published (Nieuweboer et al. Clin. Cancer Res. 2016).

Finally, in collaboration with the dept. of clinical chemistry and/or other institutes, pharmacogenetic studies are done to study dose limiting drug related toxicities (like neutropenia, diarrhea, and neurotoxicity) of chemotherapy, tyrosine kinase inhibitors (i.e. sunitinib), and supporting agents (i.e. opioids). This work is made possible by the Dutch Cancer Society and Zon Mw, among others.

   Sander Bins lab2

Sander Bins working on a translational project on sorafenib (St. Jude, February 2015)

Sander Bins ESMO 2015

Sander Bins presenting his work at the 18th ECCO/ 40th ESMO meeting (Vienna, September 2015)