Engineered platelets for the targeted destruction of circulating tumor cells - Administrative Supplement

项目总结 这项提议的目的是增加我们对使用血小板治疗的益处的理解。 防止癌症的扩散或转移。转移是癌症相关死亡的主要原因。 当一些癌细胞，也称为循环肿瘤细胞(CTCs)从原发肿瘤中分离时，就会发生这种情况 并进入血流，侵入不同位置的其他组织和器官。.的存在 患者中的CTCs与预后不良有关，因为一旦CTCs进入血液，就很难 防止它们到达次级器官并传播癌症。因此，以CTC为目标可能 代表了抗癌治疗的一个很有希望的靶点。 一旦CTC进入血液，它们就面临着许多生存挑战，包括免疫攻击， 剪切力和细胞凋亡。为了提高存活率，CTC强烈地吸引血小板形成保护性的 帮助癌细胞在血流中存活并逃脱免疫监视的斗篷。 尽管人们对血小板与循环中的肿瘤细胞相互作用的机制知之甚少，但研究表明 已经表明它们参与了癌症的进展，特别是在转移过程中，血小板帮助 降解细胞外基质(ECM)以支持癌细胞在远离 肿瘤的原始形成部位。我们建议利用血小板与循环的先天联系。 肿瘤细胞及其小分子的存储、运输和释放能力，使其成为 用于开发下一代目标和销毁CTCs的交付方法的运载工具，以 防止或尽量减少转移。

Project summary The goal of this proposal is to increase our understanding of the therapeutic benefits of using platelets for preventing the spread of cancer, or metastasis. Metastasis is the main cause of cancer-associated mortality that occurs when some cancer cells, also called circulating tumor cells (CTCs), detach from primary tumor sites and enter the bloodstream to invade other tissues and organs at different locations. The presence of CTCs in patients is associated with a poor prognosis because once CTCs enter the bloodstream it is difficult to prevent them from reaching secondary organs and spreading cancer. Therefore, targeting CTCs may represent a promising target for anticancer therapies. Once CTCs enter into the bloodstream, they face many survival challenges including immunological attack, shear forces, and apoptosis. To enhance their survival rate, CTCs strongly attract platelets to form a protective cloak that helps the cancer cells survive the forces in the bloodstream and to escape immune surveillance. Although the mechanisms by which platelets interact with circulating tumor cells are poorly understood, studies have shown that they are involved in cancer progress, especially during metastasis where platelets help to degrade extracellular matrix (ECM) to support the colonization of cancer cells in distant locations from the original tumor formation site. We propose to take advantage of platelets' innate association with circulating tumor cells and their storage, trafficking, and release capacities of small molecules, to engineer them as delivery vehicles for the development of next generation delivery methods for targeting and destroying CTCs to prevent or minimize metastasis.