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

项目摘要 这个拟议的新兴全球领导者奖(K43)的目标是提供密集的指导性研究 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保护时间， 使获奖者能够发展技能，成为一名独立资助的研究人员。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 这在很大程度上是由于缺乏与癌症相关的有效治疗的临床癌症研究活动 人口被发现了。因此，未在人群中进行测试的药物使用 在其他人群中进行的试验结果。这是不合适的，因为疾病的性质和反应 不同人群对药物的敏感性不同。LMICs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方法，这将改善 资源设置较低。这项为期五年的职业发展资助的具体目标是让 具备以下专业知识的候选人：(1)癌症相关临床工作的设计、实施和管理 试验；(2)测定血液中抗癌药物浓度的实验室方法 可用于监测治疗反应的特定分子；以及(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记物的临床试验数据。这些 将在临床试验和药物专家和平·巴巴罗拉教授的指导下实现这些目标 她将得到分子诊断专家阿比丁·奥卢瓦索拉教授的支持 尼日利亚妇女患乳腺癌的风险。我的美国导师是Olufunmilayo Olopade教授，他是 在非洲裔妇女中患乳腺癌，并在设计和实施方面拥有丰富的经验 在癌症患者中进行临床试验。我的美国合作导师是霍德正博士，他是一位发现 可用于指导癌症治疗的生物标志物。这些技能将被应用于执行 在我的导师的指导下提出的项目。拟议的项目将在#年采用临床试验方法。 尼日利亚80例标准化疗方案的有效率、毒性和生存率评估 患有侵袭性三阴性乳腺癌亚型的妇女，这种亚型在非洲更常见 并与化疗耐药性的迅速发展有关。目前，没有血迹。 用于监测治疗反应和疾病复发的测试。我们将测量血液中的microRNA水平 在治疗过程中和治疗后检测分子的变化是否可以用来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，以确保足够预期有效的肿瘤 细胞毁灭。从这个奖项中获得的技能和从这项工作中产生的数据将被用于 资助进行更多基于生物标记物的临床试验，以提供证据证明在LMIC中进行精确的癌症护理。

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.