Treatment response and microRNA profiles in triple negative breast cancer patients receiving standard chemotherapy (TARMAC)

项目摘要 这个提议的新兴全球领导者（K43）奖的目标是提供密集的指导研究 为来自低收入或中等收入国家（LMIC）的初级研究科学家提供职业支持和受保护的时间， 使获奖者能够发展成为独立资助研究人员的技能。接近70%的 低收入国家的癌症患者死于这种疾病，而高收入国家的这一比例约为30%。这是 主要是由于缺乏临床癌症研究活动，通过这些活动， 人口被发现。因此，未在人群中测试的药物使用 在其他人群中进行的试验结果。这是不适当的，因为疾病的性质和反应 对药物的依赖程度在不同人群中是不同的。中低收入国家缺乏从事临床试验活动的专家。 候选人的长期职业目标是成为设计和进行临床试验的领导者， 发现相关的、有效的和个性化的癌症治疗，这将改善癌症治疗的结果， 低资源设置。这一为期五年的职业发展补助金的具体目标是， 候选人在以下方面发展专业知识：（1）癌症相关临床的设计，实施和管理 （2）测量血液中癌症药物浓度的实验室方法以及 可用于监测对治疗的反应的特定分子;和（3）适当的统计和 生物信息学方法可用于分析和解释基于生物标志物的临床试验数据。这些 在临床试验和药物治疗专家Peace Babalola教授的指导下， 她将得到分子诊断专家AbibrillOluwasola教授的支持 尼日利亚女性患乳腺癌的几率。我的美国导师是Olufunmilayo Olopade教授，他是 她在设计和开展非洲裔妇女乳腺癌防治方案方面有着丰富的经验， 癌症患者的临床试验。我在美国的导师是霍德政博士，他是一位发现 这些生物标志物可用于指导癌症治疗。这些技能将用于执行 在我的导师的指导下提出的项目。建议的计划会采用临床试验的方法， 评估80例尼日利亚患者标准化疗方案的反应率、毒性和生存率， 患有侵袭性三阴性乳腺癌亚型的女性，这种癌症在非洲人中更为常见 女性，并与化疗耐药性的快速发展有关。目前，已无血迹 测试，以监测治疗反应和疾病复发。我们将测量血液中的微小RNA水平 在治疗期间和治疗后检测分子，以测试这些变化是否可用于指示这些患者的药物失败。 化疗药物的血液水平也将被测量，以确保它足以预期有效的肿瘤 细胞破坏。从这个奖项获得的技能和从这项工作产生的数据将用于追求 资助开展更多基于生物标志物的临床试验，为中低收入国家的精准癌症治疗提供证据。

Project Summary The goal of this proposed Emerging Global Leader (K43) Award is to provide intensive mentored research career support and protected time to a junior research scientist from a low- or middle-income country (LMIC), enabling the awardee to develop the skills to become an independently funded researcher. Close to 70% of cancer patients in LMICs die from the disease compared with about 30% in high-income countries. This is largely due to lack of clinical cancer research activities through which effective treatment relevant to the population are discovered. Consequently, medications not tested among the population are administered using trial results performed in other populations. This is inappropriate because the nature of diseases and response to drugs differ among different populations. Experts to undertake clinical trial activities are lacking in LMICs. The candidate’s long term career goal is to become a leader in designing and conducting clinical trials that will discover relevant, effective and individualized cancer therapy, which will improve cancer treatment outcome in low resource settings. The specific objectives of this five-year career development grant are to enable the candidate to develop expertise in: (1) the design, implementation and management of cancer related clinical trials; (2) laboratory methods in the measurement of the concentrations of cancer drugs in blood as well as specific molecules that can be used to monitor response to treatment; and (3) appropriate statistical and bioinformatics methods that can be used to analyze and interpret biomarker based clinical trial data. These objectives will be achieved with the mentorship of Prof. Peace Babalola, an expert in clinical trials and drug discovery, and she will be supported by Prof. Abideen Oluwasola who is an expert in the molecular diagnosis of breast cancer among Nigerian women. My USA mentor is Prof. Olufunmilayo Olopade who is an expert in breast cancer among women of African descent and has extensive experience in designing and conducting clinical trials among cancer patients. My USA co-mentor is Dr. Dezheng Huo, who is an expert in discovering biomarkers that can be used to guide cancer treatment. These skills will be applied in carrying out the proposed project under the guidance of my mentors. The proposed project will adopt a clinical trial approach in assessing the response rate, toxicity and survival rates of standard chemotherapy regimen in 80 Nigerian women with the aggressive triple negative subtype of breast cancer, which is more common among African women and is associated with rapid development of resistance to chemotherapy. At present, there is no blood test to monitor treatment response and disease relapse. We will measure the blood level of microRNA molecules during and after treatment to test if changes can be used to indicate drug failure in these patients. Blood levels of the chemotherapy drugs will also be measured to ensure it is enough to expect effective tumor cells destruction. The skills acquired from this award and data generated from this work will be used to pursue funding to conduct more biomarker-based clinical trials to provide evidence for precision cancer care in LMICs.