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.
肿瘤细胞治疗研究
英文原题:Pathophysiology and treatment of leptomeningeal metastases in lung cancer.
Pathophysiology and treatment of leptomeningeal metastases in lung cancer.
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软脑膜转移(LM)可导致恶心、头痛、神经根痛、步态障碍及颅神经麻痹等神经症状。肺癌、乳腺癌和黑色素瘤是发生软脑膜转移患者中最常见的原发肿瘤。LM发病率正在上升,可能与新疗法延长患者生存有关;部分新疗法在中枢神经系统内的效果可能较差。中枢神经系统屏障(如血脑屏障)是外周与脑之间的关键界面,可主动限制溶质和细胞进入脑实质及软脑膜。然而,癌细胞可经脑或脉络丛转移至脑膜,也可穿过软脑膜血管,或沿连接骨髓与脑膜的血管通道迁移。化疗、光子放疗和鞘内化疗等传统LM疗法疗效有限。但随着对LM病理生理认识加深及新型治疗方式出现,治疗格局正在改变。分子靶向治疗、抗体药物偶联物、免疫疗法、鞘内治疗、质子全脑脊髓照射,以及预期中的树突状细胞和NK细胞衔接疗法等近期进展,可能改善LM患者结局。本简要综述概述LM的病理生理机制和当前治疗选择。
Leptomeningeal metastases (LMs) cause neurological symptoms, including nausea, headache, radicular pain, gait disturbance, and cranial nerve palsies. Lung and breast cancer as well as melanoma are the most common primary tumors in patients with leptomeningeal metastasis.
The incidence of LMs is increasing, and this may be due to the improved survival of patients following the development of novel therapies, which may be less effective within the central nervous system. Barrier mechanisms in central nervous system such as blood-brain barrier constitute the critical interfaces between the periphery and brain that actively restrict the entry of solutes and cells into the brain parenchyma and leptomeninges.
However, cancer cells could metastasize into the meninges via the brain or choroid plexus, by crossing pial blood vessels, or through vascular channels which connect the bone marrow and meninges. Conventional treatments for LMs, such as chemotherapy, photon-based radiation therapy, and intrathecal chemotherapy, have limited efficacy.
However, advances in the understanding of the pathophysiology of LMs and novel treatment modalities are shifting this paradigm. Recent advances in molecularly targeted therapies, antibody-drug conjugates therapies, immunotherapies, intrathecal therapies, proton craniospinal irradiation, and expected therapies such as dendritic and NK cell-engaging therapies may improve the outcomes of patients with LMs. This mini review briefly outlines the pathophysiology and current treatment options for LMs.
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