Moffitt Skin Cancer SPORE

莫菲特皮肤癌孢子

• 批准号: 9134697
• 负责人: VERNON K. SONDAK
• 金额: $ 168.17万
• 依托单位: H. LEE MOFFITT CANCER CTR & RES INST
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-20 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9134697
• 关键词: Achievement; Adoptive Immunotherapy; BRAF gene; Basal Cell Cancer; Bioinformatics; Biological Assay; Biological Markers; Biology; Biometry; Cancer Center; Cancer Patient; Cells; Clinic; Clinical; Clinical Trials; Comprehensive Cancer Center; Country; Cutaneous; Cutaneous Melanoma; Cytotoxic agent; Data; Dermatology; Development; Discipline; Epidemiology; Epigenetic Process; Equine mule; Faculty; Goals; Hematology; Histones; Human Papilloma Virus Vaccine; Human Papillomavirus; Immune; Immunity; Immunology; Immunotherapy; Investigation; Laboratories; Lead; Malignant Neoplasms; Merkel Cells; Metastatic Melanoma; Metastatic/Recurrent; Modality; Movement; Mutate; Papillomavirus Infections; Pathology; Pathway interactions; Patients; Pharmaceutical Preparations; Phase; Phase II/III Trial; Play; Polyomavirus; Polyomavirus Infections; Pongidae; Prevention; Prevention trial; Preventive Intervention; Prospective Studies; Randomized; Relapse; Research; Research Infrastructure; Research Personnel; Research Project Grants; Resected; Resistance; Resources; Scientist; Signal Transduction; Skin; Skin Cancer; Skin Carcinoma; Specimen; Squamous cell carcinoma; Therapeutic; Therapeutic Intervention; Tissues; Translating; Translational Research; Tumor-Infiltrating Lymphocytes; Work; base; bench to bedside; career development; design; efficacy testing; experience; genetic analysis; immunogenicity; improved; inhibitor/antagonist; innovation; laboratory development; melanoma; mutant; novel strategies; novel therapeutics; oncology; phase III trial; pre-clinical; prevent; programs; public health relevance; success; targeted agent; targeted treatment

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.

描述(申请人提供)：Moffitt皮肤孢子的长期目标是基于我们应用于创新临床试验的实验室的发展，促进皮肤恶性肿瘤的预防和治疗方面的进步。每个项目的试验台工作是开展与孢子有关的试验的必要先导，因为这些调查将探索新的生物标志物和相关分析，这些都是每个试验翻译重要性所不可或缺的。试验的转换终点将提供新的数据，这些数据将导致实验室的进一步发展，而这些发展反过来又将反复地导致改进试验的战略。病床到病床到病床之间的互动是莫菲特作为一个独立癌症中心的核心价值所在，一个在黑色素瘤和非黑色素瘤皮肤癌管理方面拥有丰富经验的专注的临床医生和研究人员团队将与一群杰出的基础科学家合作，加速将想法从实验室转移到临床。莫菲特癌症中心及其综合黑色素瘤研究中心的支持将对实现这一目标至关重要，为确保莫菲特皮肤孢子目标的成功提供辅助资源和基础设施。在这种皮肤孢子应用中，黑色素瘤项目将专注于黑色素瘤生物学、免疫力和信号方面的研究，这些研究将创造机会，加强目前和正在开发的治疗皮肤恶性肿瘤的临床方法。项目1将为更大规模的肿瘤浸润性淋巴细胞过继免疫治疗的随机第二阶段或第三阶段试验铺平道路，以支持将BRAF药物纳入这一有希望的治疗，这是基于如何将这两种模式结合在一起的创新方法。项目2将支持在第二阶段和第三阶段试验中使用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，它使用表观遗传操作来改变我们使用免疫治疗的方式，并将证明HDAC抑制剂与ipilimumab和其他免疫刺激剂组合的第二阶段疗效测试是合理的。项目4将重点研究人类乳头状瘤病毒(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的数据将证明开发新的HPV和MCPV疫苗预防试验是正确的，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。