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

项目4由林恩马特里西安博士和惠灵顿范博士领导，重点是开发光学信标和磁共振成像 作为一种新机制的用于体内检测肿瘤相关金属蛋白酶活性的造影剂 来监测肿瘤治疗的反应基质金属蛋白酶（MMP）家族的成员涉及 与癌症侵袭相关的基质降解。有大量文献表明， 特定MMP家族成员参与与癌症相关的特定细胞过程，包括 生长因子的活化、血管生成、炎性细胞的浸润和侵袭。这些研究者 提出利用这些知识来设计一系列非侵入性体内成像试剂， 将探测肿瘤的蛋白水解状态，以帮助治疗决策，并快速评估对 标准和靶向癌症化疗。Pham博士是一名训练有素的化学家， 设计和合成了用于蛋白水解活性的光学探针，而癌症生物学家Matrisian博士 探索金属蛋白酶在小鼠癌症模型中的作用的丰富经验。的鼠模型 良性、恶性和转移性结直肠癌将用于本项目， 针对表皮生长因子（EGF）受体轴的治疗将与 项目1和项目3是ICMIC提案的一部分。

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.