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:Recent Progress in Systemic Therapy for Advanced Hepatocellular Carcinoma.
Recent Progress in Systemic Therapy for Advanced Hepatocellular Carcinoma.
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晚期肝细胞癌(HCC)患者有多种全身治疗选择。HCC有许多已知的危险因素,虽然其中一些,如丙型肝炎,现在是可以治疗的,但其他一些则无法治疗。例如,代谢功能障碍相关的慢性肝病发病率正在增加,且没有特异性治疗方法。潜在的肝病、耐药性以及在没有特异性生物标志物的情况下治疗选择不断增加,都是为每位患者选择最佳治疗方案的挑战。传统化疗几乎从不用于晚期疾病,晚期疾病转而采用免疫治疗、酪氨酸激酶抑制剂和VEGF抑制剂治疗。针对各种受体的免疫检查点抑制剂已经或正在进行临床评估。正在进行的三联药物方案试验可能是晚期HCC治疗的未来。其他免疫调节方法,如嵌合抗原受体修饰的T细胞、双特异性抗体、细胞因子诱导的杀伤细胞、NK 细胞和疫苗,正处于早期临床试验阶段。靶向治疗对HCC而言仍然有限,但代表了一个潜在的增长领域。随着我们不再将索拉非尼作为晚期HCC的一线治疗,临床试验对照组应包含索拉非尼以外的标准治疗,即作为推进疗法更好的对照。
Patients with advanced hepatocellular carcinoma (HCC) have several systemic treatment options. There are many known risk factors for HCC, and although some, such as hepatitis C, are now treatable, others are not. For example, metabolic dysfunction-related chronic liver disease is increasing in incidence and has no specific treatment. Underlying liver disease, drug resistance, and an increasing number of treatment options without specific biomarkers are all challenges in selecting the best treatment for each patient. Conventional chemotherapy is almost never used for advanced-stage disease, which instead is treated with immunotherapy, tyrosine kinase inhibitors, and VEGF inhibitors.
Immune checkpoint inhibitors targeting various receptors have been or are currently undergoing clinical evaluation. Ongoing trials with three-drug regimens may be the future of advanced-stage HCC treatment. Other immune-modulatory approaches of chimeric antigen receptor-modified T cells, bispecific antibodies, cytokine-induced killer cells, natural killer cells, and vaccines are in early-stage clinical trials.
Targeted therapies remain limited for HCC but represent an area of potential growth. As we shift away from first-line sorafenib for advanced HCC, clinical trial control arms should comprise a standard treatment other than sorafenib, one that is a better comparator for advancing therapies.
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