Project 3

该申请旨在建立unc -马拉维癌症联盟（UNC-MCC），以发展能力并开展以艾滋病毒相关癌症为重点的高影响力研究。该联盟建立在北卡罗来纳大学教堂山分校（UNC-CH）、灯塔信托基金、马拉维卫生部（MOH）和马拉维大学医学院（COM）之间的长期合作基础上。这些伙伴关系为撒哈拉以南非洲的艾滋病毒护理和预防作出了国际公认的贡献。这种基础设施现在可用于治疗与艾滋病毒相关的恶性肿瘤。UNC-MCC专注于疱疹病毒相关的癌症、卡波西肉瘤（KS）和淋巴瘤。我们的联盟将由三位具有高度互补专业知识的主要研究者领导（Satish Gopal医学博士，临床研究；Sam Phiri博士，实施科学；Blossom Damania博士，病毒学）。UNC-MCC开展的第三个研究项目试图为马拉维艾滋病毒相关淋巴瘤制定适应风险、反应导向的治疗概念。该项目由三名合作项目负责人领导。Satish Gopal （UNC马拉维项目）、Yohannie MIombe （COM）和Richard Nyasosela（卫生部）。淋巴瘤是马拉维艾滋病毒感染者中最容易治愈的癌症，该项目解决了一个核心问题，即许多患者接受的化疗可能比治愈所需的更多。在支持治疗有限的情况下，这增加了治疗相关的并发症，并危及长期生存。如果能够确定哪些患者可以用较少的化疗来治愈，就可以优化疗效和毒性之间的平衡。我们将尝试通过以下目的开发更多的风险适应和反应导向的淋巴瘤治疗方法：(1)确定马拉维hiv相关淋巴瘤患者快速实现持久临床缓解相关的临床变量和外周血生物标志物；(2)确定肿瘤特征，包括基因表达谱，这也与快速实现持久的临床缓解有关。这些目标将建立在利隆圭现有工作的基础上，作为美国国立卫生研究院资助的KCH淋巴瘤研究的一部分，由UNC-CH病毒学核心的合作者和为支持UNC-CH参与癌症基因组图谱（TCGA）项目而开发的测序基础设施加强。利用这些充足的资源，拟议的研究将产生对整个撒哈拉以南非洲艾滋病毒相关淋巴瘤护理的信息见解。

This application is to establish the UNC-Malawi Cancer Consortium (UNC-MCC), to develop capacity and conduct high-impact research focused on HIV-associated cancers. The consortium builds on longstanding collaborations between the University of North Carolina at Chapel Hill (UNC-CH), Lighthouse Trust, Malawi Ministry of Health (MOH), and University of Malawi College of Medicine (COM). These partnerships have resulted in internationally recognized contributions for HIV care and prevention in sub-Saharan Africa. This infrastructure can now be leveraged for HIV-associated malignancies. UNC-MCC is focused on the herpesvirus-associated cancers, Kaposi sarcoma (KS), and lymphoma. Our consortium will be led by three principal investigators with highly complementary expertise (Satish Gopal MD, clinical research; Sam Phiri PhD, implementation science; Blossom Damania PhD, virology). The third research project undertaken by UNC-MCC attempts to develop risk-adapted, response-guided treatment concepts for HIV-associated lymphoma in Malawi. The project is led by three co-PIs, Drs. Satish Gopal (UNC Project-Malawi), Yohannie MIombe (COM), and Richard Nyasosela (MOH). Lymphoma is the most curable cancer among HIV-infected individuals in Malawi, and this project addresses the central problem that many patients likely receive more chemotherapy than is needed to cure them. This increases treatment-related complications in a setting where supportive care is limited, and compromises long-term survival. An ability to beti:er identify patients who are curable with less chemotherapy can optimize the balance between efficacy and toxicity. We will attempt to develop more risk-adapted and response-guided approaches to lymphoma treatment through the following aims: (1) to identify clinical variables and peripheral blood biomarkers associated with rapid achievement of durable clinical remission among HIV-associated lymphoma patients in Malawi; and (2) to identify tumor characteristics, including gene expression profiles, which are also associated with rapid achievement of durable clinical remission. These aims will build on existing work in Lilongwe as part of the NIH-funded KCH Lymphoma Study, enhanced by collaborators from the UNC-CH Vironomics Core and sequencing infrastructure developed to support UNC-CH participation in The Cancer Genome Atlas (TCGA) project. Leveraging these ample resources, the proposed research will yield insights which are informative to care of HIV-associated lymphoma throughout sub-Saharan Africa.