02 - Experimental Therapeutics

摘要-实验治疗(ET)计划 概述和目标：ET计划是奥尼尔的主要翻译/临床研究引擎， 识别新靶点和开发可为创新治疗提供信息的新成像技术的目标 策略并为癌症患者提供更好的机会来改善生存，增加自由 减少疾病进展，提高生活质量。研究亮点：发现新的临床前研究 靶点，如LIMK2和PAK4，它们在临床前模型中的体内验证和药物化学努力 针对这些靶点开发临床级别的抑制剂将为三阴性提供新的治疗机会 乳腺癌(TNBC)和膀胱癌患者，对我们流域的其他癌症类型有直接影响 区域。包括缺氧和颗粒酶B在内的免疫治疗患者反应的成像标志物的研究进展 导致了乳腺癌、黑色素瘤和非小细胞肺癌的临床试验，所有这些都是重要的 在我们的集水区。继续进行成功的方案间和方案内协作，即床边工作 导致临床翻译，包括在TNBC或EGFR中与EGFR和PARP抑制的新组合 以及头颈部癌症的DNA修复检查点抑制。计划活动：ET联合领导人密切合作 与奥尼尔一起领导，通过计划活动实现计划内和计划间的协作 由孢子(子宫颈癌；P50 CA098252)和P01资金(癌症预防；P01 CA210946)加强， 通过阿拉巴马州药物发现联盟与南方研究公司的重大合作，以及 与工业界建立伙伴关系。继续与国家财团进行强有力的合作，包括NCI NCTN 领先学术伙伴网站资助(UG1 CA233330)和转化性乳腺癌研究 财团。成员：该计划有来自14个系和3所学校的60名成员。NCI的资金为360万美元， 与癌症相关的同行评审资金为780万美元，与癌症相关的资金总额为2300万美元。2065名患者 在当前CCSG周期内登记参加治疗试验，其中12%参加研究人员发起的试验，31%参加 试点/第一阶段研究，10%到第一阶段/第二阶段试验，37%到第三阶段试验。该计划有1123种出版物 在当前的CCSG周期内，包括34%的方案间、24%的方案内、68%的 与其他机构的合作，影响因子为9或更高的期刊的比例为13%。未来发展方向： 我们计划加强战略计划中列出的奥尼尔横向研究主题的现有优势， 即癌症中的肥胖和新陈代谢、癌症免疫学、成像、靶标识别和治疗 发展。我们将与社区外联和参与办公室合作，利用最近的支持 例如，跨越跨学科癌症研究连续增刊(P30 CA013148-48S6)，追赶 ETCTN附录(P30 CA013148-48S3)、基因泰克航空赠款和机构基础设施，以带来 为阿拉巴马州服务不足的人群提供最新的创新癌症治疗方法。

ABSTRACT – EXPERIMENTAL THERAPEUTICS (ET) PROGRAM Overview and Goals: The ET Program is the major translational/clinical research engine of the O'Neal with the goals of identifying novel targets and developing new imaging techniques that can inform innovative therapeutic strategies and provide cancer patients with an enhanced opportunity for improved survival, increased freedom from disease progression, and improved quality of life. Research Highlights: Discovery of new pre-clinical targets such as LIMK2 and PAK4, their in vivo validation in pre-clinical models and medicinal chemistry efforts to develop clinical grade inhibitors to these targets will provide novel therapeutic opportunities for triple-negative breast cancer (TNBC) and bladder cancer patients, with direct implications for other cancer types in our catchment area. Advances in imaging markers of patient response to immunotherapies, including hypoxia and granzyme B, have led to clinical trials in breast cancer, melanoma, and non-small cell lung cancer, all of which are of importance in our catchment area. Successful inter- and intra-programmatic collaborative bench to bedside efforts continue to result in clinical translation, including novel combinations with EGFR and PARP inhibition in TNBC or EGFR and DNA repair checkpoint inhibition in head and neck cancer. Program Activities: ET co-leaders work closely with O'Neal leadership to enable intra- and inter-programmatic collaborations through program activities enhanced by SPORE (Cervical cancer; P50 CA098252) and P01 funding (Cancer Prevention; P01 CA210946), significant collaborations with Southern Research through the Alabama Drug Discovery Alliance, and partnerships with industry. Strong collaborations with national consortia have continued, including the NCI NCTN Lead Academic Partnership Site grant (UG1 CA233330) and the Translational Breast Cancer Research Consortium. Members: The program has 60 members from 14 departments and 3 schools. NCI funding is $3.6M, cancer-relevant, peer-reviewed funding is $7.8M, and total cancer-relevant funding is $23M. 2,065 patients were enrolled in therapeutic trials over the current CCSG cycle, including 12% to investigator-initiated trials, 31% to pilot/Phase I studies, 10% to Phase I/II trials, and 37% to Phase III trials. The program had 1,123 publications over the current CCSG cycle including 34% inter-programmatic, 24% intra-programmatic, 68% resulting from collaborations with other institutions, and 13% in journals with an impact factor of 9 or greater. Future Directions: We plan to enhance current strengths in O'Neal cross-cutting research themes as laid out in the strategic plan, namely obesity and metabolism in cancer, cancer immunology, imaging, target identification and therapeutic development. We will work with the office of Community Outreach and Engagement to leverage recent support e.g., Bridge the Transdisciplinary Cancer Research Continuum supplement (P30 CA013148-48S6), CATCH-UP ETCTN supplement (P30 CA013148-48S3), Genentech AIR grant, and institutional infrastructure to bring the newest innovative cancer treatments to the underserved population of Alabama.