Sunitinib treatment requires a personalized approach, since patients can respond very differently to this drug. Pharmacogenetics may improve our ability to provide a tailored therapy by studying... Show moreSunitinib treatment requires a personalized approach, since patients can respond very differently to this drug. Pharmacogenetics may improve our ability to provide a tailored therapy by studying how genetic variations could influence drug response. The objective of this thesis was to find genetic markers that can predict toxicity and efficacy of sunitinib in patients with metastatic renal cell carcinoma. This research builds upon previous findings from candidate gene studies by testing a selection of SNPs based on plausible involvement in pharmacokinetics or pharmacodynamics of the drug of interest. We observed that SNPs located in genes involved in metabolism and drug absorption (CYP3A4, CYP3A5, and ABCB1) are potentially associated with the clearance of sunitinib and its active metabolite. In analogy to this, we confirmed SNP associations from previous studies for SNPs in CYP3A5 and ABCB1 that predict the need for dose reductions and improvement of PFS on sunitinib. Sunitinib-induced toxicity is possibly related to SNPs in CYP3A4 and CYP3A5, and in interleukin genes IL8 and IL13. VEGFR-2 (KDR) rs34231037 G-allele variant carriers were potentially associated with a favorable response to sunitinib. A GWAS learned us that SNPs in chromosome 21 are involved in sunitinib efficacy, probably by influencing drug resistance mechanisms. Show less
The goal of personalized medicine is to develop a therapy using the right drug, at the right dose, at the right time, in the right patient. Developing a novel, effective strategy for... Show moreThe goal of personalized medicine is to develop a therapy using the right drug, at the right dose, at the right time, in the right patient. Developing a novel, effective strategy for diagnosing disease in individual patients can lead to a more effective personalized approach to disease management and prevention. Traditional Chinese medicine (TCM)-based concepts, including diagnostic concepts and herbal medicine intervention, can contribute extremely valuable information regarding personalized medicine. Measuring ultra-weak photon emission (UPE) is a non-invasive method for recording the physiological state in living organisms. Delayed luminescence (DL), which is the long-term emission of photons from various materials following excitation with light, has been proposed for use in studying Chinese medicinal herbs. The studies described in this thesis were performed to develop personalized approaches to health monitoring using UPE and DL methods in combination with TCM-based concepts. The results reported in this thesis indicate both UPE and DL have high potential for studying the concepts of medicine at the systems levels, and can be used to develop future research strategies guided by TCM‒based concepts. UPE and DL will likely provide valuable new insights into personalized medicine. Show less
