Moffitt Skin Cancer SPORE

描述（由申请人提供）：莫菲特皮肤孢子的长期目标是基于我们实验室应用于创新临床试验的发展，促进皮肤恶性肿瘤预防和治疗的进展。每个项目的实验工作都是开展孢子相关试验的必要前提，因为这些研究将探索新的生物标志物和相关分析，这些都是每个试验转化重要性的组成部分。试验的转译终点将提供新的数据，这将导致进一步的实验室发展，反过来又将迭代地导致改进试验的策略。作为一家独立的癌症中心，莫菲特中心的核心价值体现了从床到床的互动。在莫菲特中心，一群在黑色素瘤和非黑色素瘤皮肤癌治疗方面拥有丰富经验的临床研究人员将与一群杰出的基础科学家合作，加速从实验室到临床的思想运动。莫菲特癌症中心及其综合黑色素瘤研究中心的支持将是实现这一目标的关键，提供辅助资源和基础设施，以确保莫菲特皮肤孢子目标的成功。在这个Skin SPORE应用程序中，黑色素瘤项目将专注于黑色素瘤生物学、免疫和信号的研究，为目前和正在开发的治疗皮肤恶性肿瘤的临床方法创造机会。项目1将为肿瘤浸润性淋巴细胞过继性免疫治疗的更大规模随机II期或III期试验铺平道路，以支持将BRAF药物纳入这一有希望的治疗中，基于如何将这两种模式结合在一起的创新方法。项目2将在II期和III期试验中支持使用Hsp90抑制剂来克服对BRAF抑制的耐药性，重新定义我们如何看待靶向治疗的耐药性。项目3代表了一种范式转变，使用表观遗传操作来改变我们使用免疫疗法的方式，并将证明HDAc抑制剂与易普利姆单抗和其他免疫兴奋剂联合的II期疗效测试是合理的。项目4将专注于人类乳头瘤病毒（HPV）和默克尔细胞多瘤病毒（MCPV）类型，它们可能在非黑色素瘤皮肤癌的发展中发挥关键作用。我们预计，项目4的数据将证明开展HPV和MCPV疫苗的新预防试验，以预防皮肤鳞状细胞癌和/或基底细胞癌。每个项目的成功和莫菲特皮肤孢子作为一个整体将对皮肤恶性肿瘤的管理产生重大影响。

DESCRIPTION (provided by applicant): The long-range goal of the Moffitt Skin SPORE is to promote progress in the prevention and treatment of cutaneous malignancies based on developments in our laboratories that are applied to innovative clinical trials. The bench work in each project is a necessary precursor to carrying out the trials associated with the SPORE, since those investigations will explore new biomarkers and correlative assays that are integral to the translational importance of each trial. The translational endpoints of the trials will provide new data that will lead to further laboratory developments that in turn will iteratively lead to strategies for improved trials. The bench-to-bedside-to-bench interaction is imbedded within the core values of Moffitt as a free-standing cancer center, in which a dedicated group of clinician-investigators with extensive experience in the management of melanoma and non-melanoma skin cancer will work with an outstanding group of basic scientists to accelerate the movement of ideas out of the laboratory to the clinic. The support of the Moffitt Cancer Center and its Comprehensive Melanoma Research Center will be crucial to fulfilling this goal, providing ancillary resources and infrastructure to insure the success of the Moffitt Skin SPORE goals. In this Skin SPORE application, the melanoma projects will focus on research in melanoma biology, immunity and signaling that create opportunities to potentiate current and developing clinical approaches to the treatment of cutaneous malignancies. Project 1 will pave the way for larger randomized phase II or phase III trials of adoptive immunotherapy with tumor infiltrating lymphocytes to support the inclusion of BRAF agents with this promising therapy, based on innovative approaches for how these two modalities should be brought together. Project 2 will support the use of Hsp90 inhibitors to overcome resistance to BRAF inhibition in phase II and III trials, redefining how we look at resistance to targeted therapies. Project 3 represents a paradigm shift that employs epigenetic manipulation to alter how we use immunotherapy, and will justify phase II efficacy testing of the combination of HDAc inhibitors with ipilimumab and other immune stimulants. Project 4 will focus on Human Papilloma Virus (HPV) and Merkel's Cell Polyoma Virus (MCPV) types that could potentially play a key role in the development of non-melanoma skin cancers. We expect that data from Project 4 will justify developing new prevention trials of vaccines for HPV and MCPV to prevent squamous and/or basal cell cancers of the skin. The success of each project and the Moffitt Skin SPORE as a whole will have a major impact on the management of cutaneous malignancies.