October 15, 2015
The 4th SOLVO Meet the Experts meeting took place in Boston last week, and featured seven speakers from industry and six from academia.
Talks were organized into three themes across two days, with the first session covering the most important pharmaceutical barriers. Xiaoyan Chu (Merck), Cory Kalvass (AbbVie), Judit Pongracz (Humeltis), and Dan Bow (AbbVie) provided an excellent series of case studies and data illustrating the importance and activity of transporters at the hepatic, blood-brain, lung, and renal barriers. Maureen Bourner (Sigma-Aldrich) then described how zinc finger nucleases are being used to generate single- and multiple-transporter knockout cell lines, using Caco-2 and MDCK cells as examples of in vitro barrier model systems in which this technology has been applied.
The second day kicked off with talks on the theme of transporter-enzyme interplay. Nathan Cherrington (U. of Arizona), Maciej Zamek-Gliszczynski (GSK), and Kevin Bush (UCSD) spoke on the topics of precision medicine and variation in transporter function, the importance of drug metabolites, and the role of transporters in signalling and homeostasis. Salman Khetani (U. of Illinois) gave a talk on the utility of using micropatterned co-cultures of hepatocytes and fibroblasts to study drug transporters and metabolizing enzymes within the same system.
In addition to improvements in longevity in culture, he detailed how the system could be used to study viral replication using hepatitis C as an example, as well as modifying the system to include Kupffer macrophases to study immunological responses, or using induced pluripotent stem cell-derived hepatocytes to provide a high-throughput screening tool that could also be used for advancements in personalized medicine.
The third session on the role of transporters in drug response and toxicity began with a talk by Michael Gottesman (NIH) on the complexity of drug resistance in cancer, which seemed particularly fitting given the approaching 30-year anniversary of the identification and cloning of the MDR1 gene by Dr. Gottesman’s lab. Michael Sawyer (U. of Alberta) then spoke about the role of uptake transporters as mediators of drug efficacy, providing several examples of nucleoside transporter inhibition by tyrosine kinase inhibitors, which may have important implications for combination therapy in cancer. Douglas Figg (NIH) who presented data on the role of OATP1B3 in androgen transport, focusing on the importance of this activity in prostate cancer, and detailing how OATP1B3-selective imaging agents could be utilized to identify metastases in prostate cancer patients.
The final talk of the meeting was given by Kenneth Brouwer (Qualyst), who detailed the importance of basolateral efflux in predicting biliary clearance and hepatotoxicity.
Attendees from industry and academia enjoyed a wealth of scientific discourse and networking opportunities during breakout sessions and meals, all within the informal but comfortable surroundings of the Boston Marriott Newton Hotel.
We would like to extend our thanks to the event sponsors for their support: Sigma-Aldrich, Qualyst Transporter Solutions, and XenoBiotic Labs. Additionally, we would also like to thank all attendees and speakers for helping to make this latest meeting a resounding success, and we hope to see you all again at the next SOLVO Meet the Experts event!
Next entry: Recorded Webinar is now avalable!