SPORE in Skin Cancer

近年来，黑色素瘤的发病率急剧上升，但没有任何治疗可以改善大多数不可切除的转移性疾病患者的总生存期。匹兹堡大学癌症研究所（UPCI）黑色素瘤和皮肤癌项目（MSCP）将继续开展卓越研究专业项目（SPORE），以提高我们对癌症进展的分子和免疫机制的理解，并验证晚期黑色素瘤和皮肤T细胞淋巴瘤（CTCL）个性化治疗的预后和预测生物标志物。在我们的4个项目中，1个项目是从上一个资助期继续进行的，3个新项目是从上一个资助期进行的开发研究中衍生出来的; 1个先前的SPORE项目将继续进行独立的投资回报率资助。我们高度整合的方法利用黑色素瘤、肿瘤学、皮肤病学、免疫学、生物统计学、生物信息学、机器学习、基因组学、蛋白质组学和生物标志物发现方面的互补专业知识，来测试对改善皮肤癌治疗结果至关重要的假设。无论临床结果如何，这些项目还将产生迫切需要的机制数据，为新的治疗策略和途径的开发提供信息，通过这些策略和途径监测复发和进展。我们的4个项目将评估：（1）与易普利姆玛和干扰素（IFN）辅助治疗相关的促炎反应和免疫抑制标志物的预后和预测价值（利用东部肿瘤协作组领导的佐剂试验）;（2）转移性黑色素瘤患者中的工程化3抗原树突状细胞疫苗和IFN？加强;（3）在转移性黑色素瘤患者中，vemurafenib调节IFN？2b免疫治疗的安全性和有效性;（4）在黑色素瘤和CTCL患者中，一种全新的个性化微针疫苗接种技术。行政核心（A）协调临床研究，并对整个SPORE进行科学和财政监督。生物标本核心（B）存放在UPCI免疫监测和细胞产品实验室，在该实验室进行所有组织建库、生物标本处理和免疫测定。生物统计学核心（C）和信息学核心（D）分别支持所有项目的数据分析和管理。我们将继续征求，审查和资助职业发展和发展研究计划的申请，这在前一个资助期导致了一个新的完整的项目设计在这个应用程序（项目3） 职业发展受益人晋升为共同调查员和项目领导人。

The incidence of melanoma has risen dramatically in recent years, but no therapy has improved overall survival for the majority of patients with unresectable metastatic disease. The University of Pittsburgh Cancer Institute (UPCI) Melanoma and Skin Cancer Program (MSCP) will continue to conduct a Specialized Program of Research Excellence (SPORE) to improve our understanding of molecular and immunologic mechanisms of cancer progression and to validate prognostic and predictive biomarkers for personalized treatment of advanced melanoma and cutaneous T cell lymphoma (CTCL). Of our 4 Projects, 1 is continued from the prior funding period, and 3 new projects have been derived from developmental research conducted in the last period; 1 of the prior SPORE projects will be continued with independent ROI funding. Our highly integrated approach leverages complementary expertise in melanoma, oncology, dermatology, immunology, biostatistics, bioinformatics, machine learning, genomics, proteomics, and biomarker discovery to test hypotheses central to the improvement of therapeutic outcome in skin cancers. Regardless of clinical outcomes, these Projects will also generate urgently needed mechanistic data to inform development of new therapeutic strategies and pathways through which to monitor relapse and progression. Our 4 Projects will evaluate: (1) the prognostic and predictive value of the pro-inflammatory response and markers of immune suppression in relation to ipilimumab and interferon (IFN)¿ adjuvant therapy (leveraging an Eastern Cooperative Oncology Group-led adjuvant trial); (2) an engineered, 3-antigen dendritic cell vaccine and IFN¿ boost in patients with metastatic melanoma; (3) the safety and efficacy of vemurafenib modulation of immunotherapy with IFN¿2b in patients with metastatic melanoma; and (4) an entirely new personalized microneedle vaccination technology in patients with melanoma and CTCL. The Administrative Core (A) coordinates the clinical research and provides scientific and fiscal oversight of the entire SPORE. The Biospecimen Core (B) is housed in the UPCI Immunologic Monitoring and Cellular Products Laboratory, where all tissue banking, biospecimen processing, and immune assays are conducted. The Biostatistics Core (C) and Informatics Core (D) support all projects with data analysis and management, respectively. We will continue to solicit, review, and fund applications for the career development and developmental research programs, which in the prior funding period led to the design of a new full project in this application (Project 3) and the promotion of career development recipients to co-investigators and a project leader.