Developmental Cancer Therapeutics

发展性癌症治疗：综述 发展性癌症治疗(DCT)计划寻求发现和描述危重癌症-- 特定的代谢途径，确定新的治疗药物，并将发现转化为有效的癌症 治疗和化学预防策略。三个共同主题统一了方案倡议：1)LID 信号和代谢，2)癌症应激反应途径，3)药物发现和早期临床 审判。在识别和机理理解方面有了根本性的发现。 鞘磷脂、前列腺素、膜受体和参与癌细胞信号传递的细胞外因子。 来自霍林斯癌症中心(HCC)的支持，在内部和跨区域共享资源和合作 这些计划导致了针对癌症新陈代谢的天然和合成化合物的识别，包括 鞘氨醇1-磷酸和鞘氨醇激酶2的抑制剂，已在#年进入1期和2期试验 难治性肾癌和肝癌(NCT01488513、NCT0176203和NCT02939807)。新化合物和 生物标志物为全州范围内的人类癌症治疗干预和预防带来了机会 影响最不发达国家集水区，包括在社会经济和地理服务不足的非洲 美国社区。该计划由30名成员组成，由两名杰出的科学家共同领导，他们拥有不同的BASIC 和临床背景合作建立一个协同计划：贝西姆·奥格雷特曼，博士，基础 在脂质生物学和生物标记物开发方面开创发现的科学家和迈克尔·礼来医学博士 内科医生-科学家将基本发现转化为临床试验。经同行评审的直接资助总额 基数，不包括职业发展和培训赠款为480万美元，有22个NCI资助的在建项目(350万美元)， 以及越来越多的多机构和方案奖(P20 GM103542；P01 CA203628；U54 MD010706、U54 CA210962)。DCT实验室中丰富的协作研究机会增强了 从少数民族院校本科生到研究生的整个教育和职业发展连续体 学生、博士后研究员和初级临床成员(K12 CA157688)。这些专注于癌症的努力 自2013年以来共出版了238份出版物，其中34%为方案内出版物，37%为方案间出版物， 67%的多机构合作，包括33项开创性发现和翻译突破 发表在顶级期刊(IF&GT；10)上，如N Engl J Med，Natural，NAT Comm，Sci Transl Med(2)，Cell， 细胞Metab、Mol Cell、JAMA(2)、JCI(3)、JCO(8)和Lancet Onol(3)。投资于尖端技术 技术、有针对性的教师招聘和新的基于团队的跨计划筹资倡议 在新的HCC领导层的支持下，DCT计划准备推进科学发现，目标是 肝癌集水区的鉴定和临床前开发，以及临床试验的实施 更远一点。

DEVELOPMENTAL CANCER THERAPEUTICS: SUMMARY The Developmental Cancer Therapeutics (DCT) Program seeks to discover and characterize critical cancer- specific metabolic pathways, identify novel therapeutic agents, and translate discoveries into effective cancer therapies and chemoprevention strategies. Three common themes unite programmatic initiatives: 1) lipid signaling and metabolism, 2) cancer stress response pathways, and 3) drug discovery and early-phase clinical trials. Fundamental discoveries have been made in the identification and mechanistic understanding of sphingolipids, prostaglandins, membrane receptors, and extra-cellular factors involved in cancer cell signaling. Support from the Hollings Cancer Center (HCC) shared resources and collaborations within and across programs has led to identification of natural and synthetic compounds that target cancer metabolism, including inhibitors of sphingosine 1-phosphate and sphingosine kinase 2, which have moved to phase 1 and 2 trials in refractory renal and liver cancers (NCT01488513, NCT0176203, and NCT02939807). New compounds and biomarkers led to statewide opportunities for therapeutic intervention and prevention of human cancers impacting the HCC catchment area, including in the socioeconomically and geographically underserved African American communities. The program of 30 members is co-led by two exceptional scientists with distinct basic and clinical backgrounds who collaboratively build a synergistic program: Besim Ogretmen, PhD, a basic scientist pioneering discoveries in lipid biology and biomarker development, and Michael Lilly, MD, a practicing physician-scientist translating fundamental discoveries into clinical trials. The total peer-reviewed direct funding base, excluding career development and training grants is $4.8M, with 22 active NCI-funded projects ($3.5M), and a growing number of multi-institutional and programmatic awards (P20 GM103542; P01 CA203628; U54 MD010706, U54 CA210962). Rich collaborative research opportunities in DCT laboratories have enhanced the entire education and career development continuum, from undergraduates in minority colleges to graduate students, postdoctoral fellows, and junior clinical members (K12 CA157688). These cancer-focused efforts culminated in 238 publications since 2013, of which 34% represent intraprogrammatic, 37% interprogrammatic, and 67% multi-institutional collaborations, including 33 seminal discoveries and translational breakthroughs published in top-tier journals (IF >10) such as in N Engl J Med, Nature, Nat Comm, Sci Transl Med (2), Cell, Cell Metab, Mol Cell, JAMA (2), JCI (3), JCO (8), and Lancet Oncol (3). With investments in cutting edge technologies, targeted faculty recruitment, and new interprogrammatic team-based funding initiatives supported by new HCC leadership, the DCT Program is poised to advance scientific discovery, target identification and pre-clinical development, and clinical trials implementation in the HCC catchment area and beyond.