(PQ9) Characterization and prophylactic treatment of chemotherapy-induced long-term adverse sequelae

癌症化疗会引起急性不良反应（如中性粒细胞减少症、恶心、脱发）， 可治疗的或暂时的。然而，临床证据表明，癌症化疗也会导致慢性 许多健康器官和组织（造血和免疫系统、中枢和外周神经系统）的损伤 系统、肺、胃肠道、心血管和生殖系统）。这些不利影响限制了 剂量的化疗药物，可以给予和削弱其疗效，以根除癌症。慢性 不良的后遗症在治疗完成后长期存在， 患者然而，化疗对功能的长期不良影响的特征 健康组织和器官，以及治疗相关疾病的原因和预防研究 才刚刚开始 国际癌症研究机构报告说， 到2025年每年1400万到1900万。由于癌症患者的长期存活率不断提高， 化疗产生长期不良后果的癌症幸存者人数正在稳步增加。 根据ACS的数据，美国目前有超过1370万癌症幸存者，预计这一数字将在2017年达到1000万。 到2022年增长到1800万。癌症患者存活率的稳步增加 化学疗法对健康组织和器官的长期影响的表征， 尽量减少它们。 这个跨学科和高度创新的项目将利用临床前乳腺肿瘤荷瘤小鼠模型 与乳腺癌的化疗以及细菌和病毒感染的小鼠模型相结合，以（1）确定 化疗对造血和免疫系统功能的长期影响及其 对新发和复发感染的反应，（2）研究炎症在引起化疗中的作用- 诱导造血和免疫系统的长期不良后遗症，并测试是否（3） 化疗和抗炎药物的同时施用，以及新的靶向递送， 化疗药物进入原发性肿瘤代表了有效的新策略，以减少或预防 化疗引起的长期不良后遗症。 这项研究的结果可以为（a）的转化和临床测试提供一个重要的平台。 作为接受化疗的癌症患者的新辅助疗法的抗炎治疗，和（B） 将化疗药物靶向递送到原发性肿瘤中作为新方法，以（1）减少 治疗相关的长期后遗症，（2）改善治疗效果，（3）提高癌症治愈率，和（4） 改善癌症患者的长期健康。

Cancer chemotherapy causes acute adverse effects (e.g. neutropenia, nausea, hair loss) which are treatable or are temporary. However, clinical evidence shows that cancer chemotherapy also causes chronic injury of many healthy organs and tissues (hematopoietic and immune systems, central and peripheral nervous system, pulmonary, gastrointestinal, cardiovascular and reproductive systems). These adverse effects limit the dose of chemotherapy drugs that can be given and diminish their efficacy to eradicate cancer. The chronic adverse aftereffects persist long after completion of therapy and jeopardize the long-term health of many patients. However, the characterization of adverse long-term effects of chemotherapy on the function of healthy tissues and organs, and the research on the causes and prevention of treatment related morbidities are just beginning. The International Agency for Cancer Research reported that the number of new cancer cases will rise from 14 to 19 million per year by 2025. Since the long-term survival rates of cancer patients continue to improve, the number of cancer survivors with long-term adverse consequences from chemotherapy is steadily increasing. According to ACS there are now over 13.7 million cancer survivors in the US, with that number expected to grow to 18 million by 2022. Steady increase in the frequency of patients surviving cancer necessitates characterization of long-term effects of chemotherapy on healthy tissues and organs and finding approaches to minimize them. This interdisciplinary and highly innovative project will utilize preclinical breast tumor-bearing mouse models combined with chemotherapy for breast cancer and mouse models of bacterial and viral infections to (1) define long-lasting effects of chemotherapy on the function of hematopoietic and immune systems and their responses to new and recurring infections, (2) investigate the role of inflammation in causing chemotherapy- induced long-term adverse sequelae in the hematopoietic and immune systems, and test whether (3) concurrent administration of chemotherapy and anti-inflammatory drugs, and novel targeted delivery of chemotherapy drugs into the primary tumors represent effective new strategies to decrease or prevent chemotherapy-induced long-term adverse sequelae. The outcomes of this research could provide a significant platform for translational and clinical testing of (a) anti-inflammatory treatment as new adjunct therapy for cancer patients undergoing chemotherapy, and (b) novel targeted delivery of chemotherapy drugs into the primary tumors as new approaches to (1) reduce treatment-related long-term sequelae, (2) improve treatment efficacy, (3) increase cancer cure rate, and (4) improve the long-term health of cancer patients.