CaseReport-Thalidomideandhyperkalemia.pptVIP

mTOR inhibitors for cancer in future 1. Optimal drug administration 2. Markers of sensitivity and resistance 3. Combination of targeted agents 4. Development of more-effective mTOR inhibitors mTOR kinase inhibitors Introduction to mTOR inhibitors mTOR signaling pathway mTOR inhibitors and transplant mTOR inhibitors and cancer Current development of mTOR inhibitors Conclusion Conclusion-1 mTOR is a central regulator of cell proliferation In some tumor types, such as RCC and certain lymphomas, mTOR as key role in tumor cell proliferation and angiogenesis Temsirolimus and everolimus are approved as monotherapy in advanced RCC Conclusion-2 Temsirolimus also approved in MCL with notable improvement in PFS Biomarkers to identify tumor types that are sensitive to mTOR inhibition Combination target therapy augment anti-tumor activity and overcoming resistance PFS: progression-free survival Recommendations In vivo concentration of endoxifen needed to maximally inhibit breast cancer proliferation is unknown Potent CYP2D6 inhibitors be avoided in women receiving tamoxifen (Strong) When the use of a drug known to potently inhibit CYP2D6 is necessary, consideration should be given to treat with the inhibitor for the shortest period of time possible. (Weak) Thank you for your attention !! 血液腫瘤科實習報告 藥理學研究所 臨床藥學組 碩一 黃瑩瑀 指導醫師：趙大中 醫師 2012.04.16 * * Rapamycin最早是1975年在復活島上泥土的樣本中發現，從Streptomyces hygroscopicus 提取的巨環抗生素，嬌生公司還在發現處立一面紀念牌紀念rapamycin的發現。 Rapamycin原先發展當作抗黴菌藥，因療效不佳又具有免疫抑制作用而發展成免疫抑制劑 第一個Rapa類藥物是Sirolimus在1999年美國FDA通過的Rapamune?，用來預防器官移植後排斥。 * mTOR inhibitor 目前已發展出四種藥品分別為Sirolimus, Everolimus, Temsirolimus, Ridaforolimus 另外有小分子的mTOR kinase inhibitors 還在phase I 研究中。 mTOR inhibitor 具有免疫抑制與抗細胞增生的作用，目前臨床運用在三個方面 1. 預防器官移植後排斥作用的免疫抑制劑 (目前核准用於心臟/腎臟移植) 2. 冠心病的塗藥支架 3. 抗腫瘤藥物(目前核准用於RCC/MCL) * 本類似種藥品結構大致相同，新藥都是在Sirolimus的第42個碳上做modify (addition of an ester, ether, or phosphonate group) ，以增加溶解度，提高生體可用率? * Sirolimus是口服劑型，用在預防器官移植排斥，半衰期長，生體可用率差 Everolimus是口服劑型，Certican 0.5 m