Point-of-Care Microfluidics in Lung Cancer

描述(申请人提供)：原发肿瘤的细胞以远处器官转移的形式扩散是导致90%与癌症相关的死亡的原因，仅在美国每年就有超过50万人死亡。因此，转移是癌症研究领域需要解决的最重要的生物学问题之一。尽管外周血中循环肿瘤细胞(CTCs)的形式已经在原发恶性肿瘤和周围转移之间建立了细胞联系，但在破译这一非常独特的细胞群体的生物学方面仍然存在重大挑战，并最终提高我们系统水平对癌症如何扩散和死亡的理解。对于肺癌尤其如此，肺癌是美国癌症死亡的主要原因，也将是我们提出的量子计划的主要重点。鉴于超过85%的主要癌症，包括肺癌，起源于其上皮细胞，我们将关注转移性肺癌患者外周血中存在的上皮性CTCs。然而，我们需要克服“高风险”和尚未得到满足的关键技术挑战，即有效分离全血中频率低至1/10e9的CTCs的细胞分选技术。为了应对这一尚未解决的技术挑战，我们计划开发一种新的护理点式一次性微芯片技术，能够以每秒100万到1000万个细胞的速度选择性分离稀有CTCs，并最终将微流控技术引入临床癌症药物(总目标)。人体研究将被优先考虑，并将为我们的技术创新提供严格的考验。这是一个哲学上的决定，因为参与该项目的研究团队强烈认为，量子项目的愿景，即在8到10年的时间段内使用技术驱动的方法解决或深刻改善特定的健康状况，必须在计划开始时将重点放在真实的系统上。使用老鼠和其他动物模型的癌症生物学已经取得了很大进展，但人们也认识到这种模仿(如何)有很大的局限性。这种护理点式微芯片血液活检有可能通过肺癌的早期分子诊断、识别新的生物标记物来预测癌症结果的好坏，最终为进一步的基础和临床研究提出新的靶点，以及癌症药物干预和免疫治疗的富有成效的靶点，从而改变肺癌患者的护理。

DESCRIPTION (provided by applicant): Dissemination of cells from the primary tumor in the form of metastasis in distant organs is responsible for 90% of the cancer-related deaths, representing over 500,000 people dying every year in the United States alone. Consequently, metastases are among the most important biological problem to address in the area of cancer research. Although a cellular link between the primary malignant tumor and the peripheral metastases has been established in the form of circulating tumor cells (CTCs) in peripheral blood, a major challenge remains in deciphering the biology of this very unique cellular population, and ultimately, improving our systems level understanding of "how cancer spreads and kills". This is especially true for lung cancer, the leading cause of cancer deaths in the United States and will be the primary focus of our proposal for the Quantum Project. Given that more than 85% of major cancers, including lung cancer, originate from their epithelial cells, our focus will be the epithelial CTCs present in peripheral blood of the patients with metastatic lung cancer. However, we need to overcome a "high-risk" and critical unmet technological challenge, namely cell sorting technology for efficient isolation of CTCs with frequencies as low as 1 in 10e9 in whole blood. To address this unmet technological challenge, we plan to develop a new point-of-care, disposable microchip technology capable of selective separation of rare CTCs at a rate of 1 to 10 million cells per second, and to ultimately introduce microfluidic technologies to clinical cancer medicine (Overall Goal). Human studies will be given priority and will provide rigorous test of our technological innovations. This is a philosophical decision in that the team of investigators involved in this project strongly believe that the vision of the Quantum Project, namely, solving or profoundly improving a specific health condition using technology-driven approaches in a time period of 8 to 10 year must have a sharp focus on real systems at the onset of the program. Much progress has occurred in cancer biology using mouse and other animal models, but it is also recognized that there are significant limits to this mimicry (How). This point-of-care microchip blood biopsy has the potential to transform lung cancer patient care through early molecular diagnosis of lung cancer, the identification of new biomarkers to predict outcomes both good and bad in cancer, and finally, suggest new targets for further basic and clinical research, as well as fruitful targets for pharmacological interventions and immunotherapy in cancer (Future Benefits).