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

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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.