We congratulate Masturah Bte Mohd Abdul Rashid, a PhD student from Dr Edward Chow’s group, for receiving both the SLAS Tony B. Travel Award and SLAS 2016 Best Student Poster Award at the SLAS 2016 Conference.
SLAS 2016 Conference is an annual gathering of life sciences R&D professionals dedicated to discovery and technology. It was held at the San Diego Convention Center in San Diego, CA, USA from 23-27 January 2016 and highly participated by 6,293 participants.
Masturah is honored to be selected as one of the three participants to receive the Best Student Poster Award, sharing the same title with students from Harvard University and Griffith University of Australia.
Congratulations to Masturah Rashid!
Synergistic Combinations Against Bortezomib-Resistant Multiple Myeloma Derived via Phenotypic Personalized Medicine (PPM)
Masturah Bte Mohd Abdul Rashid1,2*, Tan Boon Toh1, Lissa Nurrul Abdullah1, Aleidy Silva3, Wee Joo Chng2,4 and Edward Kai-Hua Chow1,2
1Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
2Cancer Science Institute of Singapore, National University of Singapore
3Department of Mechanical and Aerospace Engineering, University of California, Los Angeles, Los Angeles, CA, USA
4Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Multiple myeloma, the second most frequent hematological malignancy, is a plasma cell malignancy that arises from intramedullary tumour sites. Despite advancements in treatment, 5-year overall survival for multiple myeloma still remains below 50% and the rates of relapse remain relatively high1. Tumor heterogeneity leads to the emergence of different clones, which confers tumor resistance to the current drug treatment and hence raises the importance of combinatorial drug therapy. However, the currently available multidrug regimens for multiple myeloma are usually additively determined. Coupled with the vast combinatorial dosing space and inherent complexity of biological systems, it is challenging to come up with optimal dosages for each drug. In order to bridge this gap, we utilized phenotypic personalized medicine (PPM) to objectively identify optimal drug combinations that would be able to target the desired system of interest. PPM aims to project interactions between drugs via response surface maps. It has been used for inhibition of viral activity, maintenance of human embryonic stem cells as well as drug optimization for cancer, where we have successfully highlighted optimal drug combinations in hepatocellular carcinoma2. In this study, we aim to establish optimal drug combinations that are efficacious against Bortezomib-resistant multiple myeloma by harnessing PPM as an aiding tool. PPM was carried out in vitro and in vivo assays were used to validate the results derived in vitro. We have successfully identified potential optimal drug combinations for Bortezomib-resistant RPMI 8226 as projected via PPM, with both combinations exhibiting synergistic response surface maps. In vitro validation using viability assays support these combinations where the drug combinations displayed a lower half-maximal inhibitory concentration (IC50) as compared to single drug administration. As an indicator of drug interactions, combination indices (CI) are widely used and calculated via the Chou-Talaylay method3. The CI of the optimal combinations indicated synergistic, supporting the combinations generated via PPM. Furthermore, preliminary elucidation of the mechanisms driving these drug combinations validates the identified drug combinations. Thus, these results collectively show that PPM is a robust platform that is able to eradicate the Bortezomib-resistant clones of multiple myeloma and the drug combinations highlighted could serve as potential therapeutic options.