3-S22-1
腫瘍循環器学−がん治療ならびにがん悪液質によって起こる心機能障害発現メカニズムの解明−
Cardio-oncology -Elucidation of the mechanism of cardiac dysfunction caused by cancer therapy and cancer cachexia-
〇野中 美希1、上園 保仁1,2
Miki Nonaka1, Yasuhito Uezono1,2
1国立がん研、2国立がん研究センター中央病院先端医療開発センター 支持療法開発分野
1Div. Pathophysiol., Natl. Cancer Ctr. Res. Inst., 2Ctr. Suppo. Palliat. Psycho. Care, Natl Cancer Ctr. Hosp.
Cancer patients nowadays can choose a wide variety of cancer therapies based on new anti-cancer drugs and state-of-the art operational technology. Also, cancer has been recognized as curable diseases with increased cancer survivors. On the other hand, cancer survivors who have various problems during and after treatment of cancer therapy are increasing. Recently, as an increase in the number of cancer survivors, emphasis has been placed on the importance of development of survivors' QOL such as cardiovascular disorders occurred in cancer survivors. Indeed, certain anticancer drugs and molecular targeted therapies induce cardiotoxicity, which limit the widespread implementation of cancer treatment and significant decrease of QOL in cancer patients. In addition, cardiac dysfunction induced by cancer cachexia has also been reported. In view of these backgrounds, it is necessary to clarify the dynamics of cardiovascular system of cancer survivors and patients with cancer cachexia, to prevent cardiac dysfunction accompanying with cancer therapy and cachexia. Quite recently, interdisciplinary research area namely Cardio-oncology has been established to try to solve these issues. In the present study, we will present anticancer drug-induced cardiotoxicity and cardiac dysfunction occurring in cancer cachexia, and discuss our research approaches and data to understand such pathophysiology and possible prevention and therapies.
3-S22-2
ヒトiPS細胞技術を活用した抗がん剤の心毒性評価系の開発
Human iPS cell technology as non-clinical tools for predicting cardio-oncology therapy side effects
〇諫田 泰成1
Yasunari Kanda1
1国立医薬品食品衛研・薬理部
1Div Pharmacol, NIHS
As cancer patients live longer, it is important to recognize cardiotoxicity that induce electrophysiological or structural changes by many oncology drugs, such as anthracyclines and tyrosine kinase inhibitors. Thus, understanding of cardio-oncology (also known as onco-cardiology) is more critical for the effective care of cancer patients. Huma induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been widely used to evaluate cardiotoxicity as highly physiologically relevant human cells. We all-japan consortium have proposed a new proarrhythmia risk assessment method using hiPSC-CMs by our large-scale validation study. In addition to proarrhythmia risk, it is necessary to detect other type of side effects, such as chronic effects and impaired contractility from the viewpoint of cardio-oncology. To investigate how to use hiPSC-CMs for oncology drugs, we have attempted to make standardized protocols for long-term effects of drugs using motion vector system. In the symposium, I would like to share our recent data and discuss future perspectives for the usage of hiPSC-CMs in the cardio-oncology field.
3-S22-3
心筋細胞のDNA損傷応答におけるDNAメチル化制御機構の役割
The role of DNA methylation in anticancer drug-induced DNA damage repair system in cardiomyocytes.
〇細田 洋司1
Hiroshi Hosoda1
1国立循環器病研究センター研究所再生医療部
1Dept. Regenerative Medicine and Tissue Engineering, NCVC Research Institute
Genomic DNA, which contains all of the genetic information, is damaged by a variety of endogenous and environmental factors such as genotoxic chemicals, ionizing radiation and UV light. Consequently, the DNA repair process is constantly active as it responds to damage in the DNA structure. Not only cardiotoxicity of anticancer drug treatment but also ischemic heart disease and heart failure associated with overloaded pressure interfere with DNA damage response and DNA repair regulation in cardiomyocytes. DNA methylation, catalyzed by the DNMTs, plays an important role in maintaining genome stability, but the molecular mechanism is not clear. In this study, we examine and outline the links between DNA methylation and the DNA damage repair systems and discuss the possible mechanisms of how they are orchestrated, with a focus on cardiotoxicity of anticancer drugs.
3-S22-4
重要性を増す Cardio-Oncology : 新たな学際領域研究の現状と今後の方向性
Cardio-Oncology: Challenges and Opportunities in the New Interdisciplinary Research
〇佐瀬 一洋1,2
Kazuhiro Sase1,2
1順天堂大学大学院医学研究科、2早稲田大学重点領域研究機構医療レギュラトリーサイエンス研究所
1Clin. Pharm. & Reg. Sci., Juntendo Univ., 2Inst. for Med. Reg. Sci., Waseda Univ.
Advances in cancer treatment have led to dramatic increase in cancer survivors.
Although cardiotoxicity resulting from anthracyclines and radiation therapies has been known for decades, the emergence of novel cancer treatment-related cardiovascular diseases (CTRCD) have been recognized to be associated with molecularly targeted therapies as well as immune checkpoint inhibitors.
Cardio-Oncology is a new interdisciplinary research opportunity at the intersection of cardiovascular disease and cancer.
Research priorities need to be identified to diagnose, treat, and prevent the previously unknown CTRCD(s), including (1) myocardial dysfunction and heart failure, (2) coronary artery disease, (3) valvular disease, (4) arrhythmias and QT-prolongation, (5) arterial hypertension, (6) thromboembolic disease and others.
For example, understanding fundamental mechanisms underlying CTRCD is essential to the development of new methods to manage these toxicities. The application of more suitable disease models and more effective methods for toxicity screening will serve to advance our understanding of CTRCD. Animal models have been successfully employed to predict potential problems in some cases, but more highly predictive models are also needed. Biobanks and other specimens with patient registries would facilitate the validation of biomarkers, genome analysis, and imaging methods.