Tumor priming sequences combined with novel nanoparticle drug carriers for enhanced therapeutic efficacy in pancreatic cancer: a tripartite USA/Northern Ireland/Republic of Ireland consortium

肿瘤启动序列与新型纳米颗粒药物载体相结合，增强胰腺癌的治疗效果：美国/北爱尔兰/爱尔兰共和国三方联盟

• 批准号: MC_PC_15013
• 负责人: Christopher Scott
• 金额: $ 19.11万
• 依托单位: Queen's University Belfast
• 依托单位国家: 英国
• 项目类别: Intramural
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MC_PC_15013
• 关键词: Tumor; priming; sequences; combined; novel

Pancreatic cancer is lethal to the vast majority of patients, largely because the disease is advanced when discovered, and tumor blood flow is so low that drugs do not readily access the tumor. This project will address the ‘drug delivery’ barrier by establishing a conceptual understanding of how ‘tumor priming’ agents work; they attack the barrier between the blood stream and the tumor interior, creating a ‘window of opportunity’ for delivery of a second agent. We hypothesize that nanoparticle-based drug carriers may have unique advantages that enable them to exploit tumor priming strategies more effectively and improve therapeutic outcomes; inclusion of several clinically-approved agents in our research plan will provide strong rationale for near-term clinical trials in pancreatic cancer, and we propose novel novel nanoparticle agents of longer-term developmental potential.

胰腺癌对绝大多数患者来说是致命的，主要是因为该疾病在发现时已是晚期，而且肿瘤血流非常低，药物无法轻易进入肿瘤。该项目将通过建立对“肿瘤启动”剂如何发挥作用的概念性理解来解决“药物输送”障碍；它们攻击血流和肿瘤内部之间的屏障，为第二种药物的输送创造“机会之窗”。我们假设基于纳米颗粒的药物载体可能具有独特的优势，使它们能够更有效地利用肿瘤启动策略并改善治疗结果；在我们的研究计划中纳入几种临床批准的药物将为胰腺癌的近期临床试验提供强有力的理由，并且我们提出了具有长期发展潜力的新型纳米颗粒药物。

项目成果

USP17 is required for trafficking and oncogenic signaling of mutant EGFR in NSCLC cells.

• DOI: 10.1186/s12964-018-0291-5
• 发表时间: 2018-11-08
• 期刊: Cell communication and signaling : CCS
• 作者: McCann AP;Smyth P;Cogo F;McDaid WJ;Jiang L;Lin J;Evergren E;Burden RE;Van Schaeybroeck S;Scott CJ;Burrows JF
• 通讯作者: Burrows JF

Controlled coupling of an ultrapotent auristatin warhead to cetuximab yields a next-generation antibody-drug conjugate for EGFR-targeted therapy of KRAS mutant pancreatic cancer.

• DOI: 10.1038/s41416-020-01046-6
• 发表时间: 2020-11
• 期刊: British journal of cancer
• 影响因子: 8.8
• 作者: Greene MK;Chen T;Robinson E;Straubinger NL;Minx C;Chan DKW;Wang J;Burrows JF;Van Schaeybroeck S;Baker JR;Caddick S;Longley DB;Mager DE;Straubinger RM;Chudasama V;Scott CJ
• 通讯作者: Scott CJ

Forming next-generation antibody-nanoparticle conjugates through the oriented installation of non-engineered antibody fragments.

通过非工程抗体片段的定向安装形成下一代抗体-纳米颗粒缀合物。

• DOI: 10.1039/c7sc02747h
• 发表时间: 2018-01-07
• 期刊: Chemical science
• 影响因子: 8.4
• 作者: Greene MK;Richards DA;Nogueira JCF;Campbell K;Smyth P;Fernández M;Scott CJ;Chudasama V
• 通讯作者: Chudasama V