RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Precision Medicine for Colorectal Cancer with Liquid Biopsy and Immunotherapy.
Precision Medicine for Colorectal Cancer with Liquid Biopsy and Immunotherapy.
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在结直肠癌(CRC)治疗领域,过去二十年中诊断方法和化疗方案取得了显著进展。然而,识别肿瘤复发/再发早期检测所需的最小残留病(MRD),并在肿瘤变得多药耐药和更具侵袭性之前及时选择并提供合适的药物,仍然十分困难。我们认为,利用肿瘤的深入基因组图谱是进一步提高CRC患者总体预后的重大突破。随着方法学和生物信息学方面的最新技术进步,可以通过基于血液的检测——液体活检——毫不延迟地深入分析基因组图谱。从临床角度来看,微创液体活检被认为是一种有前景的方法,可以应用于常规临床环境,以满足未满足的临床需求。在这篇综述中,我们强调了液体活检在CRC患者临床管理中的临床实用性,包括癌症筛查、MRD检测、合适分子靶向药物的选择、治疗反应性监测以及疾病复发/再发的极早期检测。此外,我们还探讨了过继性T细胞疗法以及基于肿瘤基因组信息的未来个性化免疫治疗的可能性。
In the field of colorectal cancer (CRC) treatment, diagnostic modalities and chemotherapy regimens have progressed remarkably in the last two decades.
However, it is still difficult to identify minimal residual disease (MRD) necessary for early detection of recurrence/relapse of tumors and to select and provide appropriate drugs timely before a tumor becomes multi-drug-resistant and more aggressive.
We consider the leveraging of in-depth genomic profiles of tumors as a significant breakthrough to further improve the overall prognosis of CRC patients. With the recent technological advances in methodologies and bioinformatics, the genomic profiles can be analyzed profoundly without delay by blood-based tests-'liquid biopsies'.
From a clinical point of view, a minimally-invasive liquid biopsy is thought to be a promising method and can be implemented in routine clinical settings in order to meet unmet clinical needs. In this review, we highlighted clinical usefulness of liquid biopsies in the clinical management of CRC patients, including cancer screening, detection of MRD, selection of appropriate molecular-targeted drugs, monitoring of the treatment responsiveness, and very early detection of recurrence/relapse of the disease.
In addition, we addressed a possibility of adoptive T cell therapies and a future personalized immunotherapy based on tumor genome information.
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