Proteolytic Beacons in the Non-invasive Assessment of Response to Cancer Therapy

项目4由Lynn Matrisian博士和Wellington Pham博士领导，专注于开发光学信标和核磁共振 作为一种新机制的造影剂用于体内检测肿瘤相关金属蛋白酶活性 监测对肿瘤治疗的反应。基质金属蛋白酶(MMPs)家族成员参与了 与癌症侵袭相关的基质降解。有大量文献表明 特定的基质金属蛋白酶家族成员参与与癌症相关的特定细胞过程，包括 生长因子的激活、血管生成、炎性细胞的渗透和侵袭。这些调查人员 建议利用这一知识设计一系列非侵入性体内成像试剂， 将探测肿瘤的蛋白质分解状态，以帮助治疗决策，并快速评估对 标准的和有针对性的癌症化疗。范博士是一名训练有素的化学家，他带来了丰富的经验 通过设计和合成用于蛋白质分解活性的光学探针，癌症生物学家马特里西安博士已经 探索金属蛋白酶在小鼠癌症模型中的作用的丰富经验。小鼠模型的建立 良性、恶性和转移性结直肠癌将在这个项目中使用，对癌症的反应 针对表皮生长因子(EGF)受体轴的治疗将与 这项ICMIC提案的项目1和3。

Project 4, led by Drs. Lynn Matrisian and Wellington Pham, focuses on developing optical beacons and MRI contrast agents for the in vivo detection of tumor-associated metalloproteinase activity as a novel mechanism to monitor response to tumor therapy. Members of the matrix metalloproteinase (MMP) family are implicated in the matrix degradation associated with cancer invasion. There is substantial literature indicating the involvement of specific MMP family members in specific cellular processes related to cancer, including the activation of growth factors, angiogenesis, infiltration of inflammatory cells, and invasion. These investigators propose to take advantage of this knowledge to devise a series of non-invasive in vivo imaging reagents that will probe the proteolytic status of a tumor to aid in treatment decisions, and rapidly assess the response to standard and targeted cancer chemotherapies. Dr. Pham, a chemist by training, brings extensive experience with the design and synthesis of optical probes for proteolytic activity, and Dr. Matrisian, a cancer biologist, has extensive experience exploring the role of metalloproteinases in mouse models of cancer. Murine models of benign, malignant, and metastatic colorectal cancer will be used in this project, and the response to cancer therapies directed at the epidermal growth factor (EGF) receptor axis will be tested in collaboration with projects 1 and 3 of this ICMIC proposal.