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Clinical and molecular significance of homologous recombination deficiency positive non-small cell lung cancer in Chinese population: An integrated genomic and transcriptional analysis. 同源重组缺陷阳性非小细胞肺癌在中国人群中的临床和分子意义:基因组和转录的综合分析
IF 7 2区 医学 Q1 ONCOLOGY Pub Date : 2024-06-30 DOI: 10.21147/j.issn.1000-9604.2024.03.05
Yifei Wang, Yidan Ma, Lei He, Jun Du, Xiaoguang Li, Peng Jiao, Xiaonan Wu, Xiaomao Xu, Wei Zhou, Li Yang, Jing Di, Changbin Zhu, Liming Xu, Tianlin Sun, Lin Li, Dongge Liu, Zheng Wang

Objective: The clinical significance of homologous recombination deficiency (HRD) in breast cancer, ovarian cancer, and prostate cancer has been established, but the value of HRD in non-small cell lung cancer (NSCLC) has not been fully investigated. This study aimed to systematically analyze the HRD status of untreated NSCLC and its relationship with patient prognosis to further guide clinical care.

Methods: A total of 355 treatment-naïve NSCLC patients were retrospectively enrolled. HRD status was assessed using the AmoyDx Genomic Scar Score (GSS), with a score of ≥50 considered HRD-positive. Genomic, transcriptomic, tumor microenvironmental characteristics and prognosis between HRD-positive and HRD-negative patients were analyzed.

Results: Of the patients, 25.1% (89/355) were HRD-positive. Compared to HRD-negative patients, HRD-positive patients had more somatic pathogenic homologous recombination repair (HRR) mutations, higher tumor mutation burden (TMB) (P<0.001), and fewer driver gene mutations (P<0.001). Furthermore, HRD-positive NSCLC had more amplifications in PI3K pathway and cell cycle genes, MET and MYC in epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) mutant NSCLC, and more PIK3CA and AURKA in EGFR/ALK wild-type NSCLC. HRD-positive NSCLC displayed higher tumor proliferation and immunosuppression activity. HRD-negative NSCLC showed activated signatures of major histocompatibility complex (MHC)-II, interferon (IFN)-γ and effector memory CD8+ T cells. HRD-positive patients had a worse prognosis and shorter progression-free survival (PFS) to targeted therapy (first- and third-generation EGFR-TKIs) (P=0.042). Additionally, HRD-positive, EGFR/ALK wild-type patients showed a numerically lower response to platinum-free immunotherapy regimens.

Conclusions: Unique genomic and transcriptional characteristics were found in HRD-positive NSCLC. Poor prognosis and poor response to EGFR-TKIs and immunotherapy were observed in HRD-positive NSCLC. This study highlights potential actionable alterations in HRD-positive NSCLC, suggesting possible combinational therapeutic strategies for these patients.

目的:同源重组缺陷(HRD)在乳腺癌、卵巢癌和前列腺癌中的临床意义已经确立,但HRD在非小细胞肺癌(NSCLC)中的价值尚未得到充分研究。本研究旨在系统分析未经治疗的 NSCLC 的 HRD 状态及其与患者预后的关系,以进一步指导临床治疗:方法:共回顾性纳入了355例未经治疗的NSCLC患者。HRD状态使用AmoyDx基因组疤痕评分(GSS)进行评估,评分≥50分为HRD阳性。分析了HRD阳性和HRD阴性患者的基因组、转录组、肿瘤微环境特征和预后:结果:HRD阳性患者占25.1%(89/355)。与HRD阴性患者相比,HRD阳性患者有更多的体细胞致病性同源重组修复(HRR)突变,肿瘤突变负荷(TMB)更高(表皮生长因子受体(EGFR)/无性淋巴瘤激酶(ALK)突变NSCLC中的PMET和MYC,以及EGFR/ALK野生型NSCLC中更多的PIK3CA和AURKA)。HRD阳性的NSCLC显示出更高的肿瘤增殖和免疫抑制活性。HRD阴性NSCLC显示出主要组织相容性复合体(MHC)-II、干扰素(IFN)-γ和效应记忆CD8+ T细胞的活化特征。HRD阳性患者的预后较差,接受靶向治疗(第一代和第三代表皮生长因子受体抑制剂-TKIs)后的无进展生存期(PFS)较短(P=0.042)。此外,HRD阳性、表皮生长因子受体/ALK野生型患者对无铂免疫治疗方案的反应较低:结论:在HRD阳性NSCLC中发现了独特的基因组和转录特征。HRD阳性NSCLC预后差,对表皮生长因子受体抑制剂(EGFR-TKIs)和免疫疗法反应差。这项研究强调了HRD阳性NSCLC中潜在的可操作改变,为这些患者提出了可能的联合治疗策略。
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引用次数: 0
Unlocking epigenetics for precision treatment of Ewing's sarcoma. 解开表观遗传学,精准治疗尤文氏肉瘤。
IF 7 2区 医学 Q1 ONCOLOGY Pub Date : 2024-06-30 DOI: 10.21147/j.issn.1000-9604.2024.03.08
Zhehao Fan, Shuangshuang Dong, Ning Wang, Muhammad Babar Khawar, Jingcheng Wang, Haibo Sun

Ewing's sarcoma (EWS) is a highly aggressive malignant bone tumor primarily affecting adolescents and young adults. Despite the efficacy of chemoradiotherapy in some cases, the cure rate for patients with metastatic and recurrent disease remains low. Therefore, there is an urgent need for innovative therapeutic approaches to address the challenges associated with EWS treatment. Epigenetic regulation, a crucial factor in physiological processes, plays a significant role in controlling cell proliferation, maintaining gene integrity, and regulating transcription. Recent studies highlight the importance of abnormal epigenetic regulation in the initiation and progression of EWS. A comprehensive understanding of the intricate interactions between EWS and aberrant epigenetic regulation is essential for advancing clinical drug development. This review aims to provide a comprehensive overview of both epigenetic targets implicated in EWS, integrating various therapeutic modalities to offer innovative perspectives for the clinical diagnosis and treatment of EWS.

尤文氏肉瘤(EWS)是一种侵袭性很强的恶性骨肿瘤,主要影响青少年和年轻人。尽管化放疗在某些病例中疗效显著,但转移性和复发性患者的治愈率仍然很低。因此,迫切需要创新的治疗方法来应对与 EWS 治疗相关的挑战。表观遗传调控是生理过程中的一个关键因素,在控制细胞增殖、维持基因完整性和调节转录方面发挥着重要作用。最近的研究强调了表观遗传调控异常在 EWS 发病和进展过程中的重要性。全面了解 EWS 与表观遗传调控异常之间错综复杂的相互作用对于推进临床药物开发至关重要。本综述旨在全面概述与 EWS 有关的两个表观遗传靶点,整合各种治疗模式,为 EWS 的临床诊断和治疗提供创新视角。
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引用次数: 0
Tislelizumab in previously treated, locally advanced unresectable/metastatic microsatellite instability-high/mismatch repair-deficient solid tumors. Tislelizumab 用于既往接受过治疗的局部晚期不可切除/转移性微卫星不稳定性高/错配修复缺陷实体瘤。
IF 7 2区 医学 Q1 ONCOLOGY Pub Date : 2024-06-30 DOI: 10.21147/j.issn.1000-9604.2024.03.03
Jian Li, Ye Xu, Aimin Zang, Yunong Gao, Quanli Gao, Yanqiao Zhang, Dong Wang, Jianming Xu, Ying Yuan, Haiping Jiang, Jieer Ying, Chunmei Shi, Yanhong Deng, Jing Wang, Tianshu Liu, Yi Huang, Xiaoping Qian, Yueyin Pan, Ying Cheng, Sheng Hu, Jin Wang, Mengyue Shi, Ke Wang, Han Hu, Lin Shen

Objective: The open-label, phase II RATIONALE-209 study evaluated tislelizumab (anti-programmed cell death protein 1 antibody) as a tissue-agnostic monotherapy for microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) tumors.

Methods: Adults with previously treated, locally advanced unresectable or metastatic MSI-H/dMMR solid tumors were enrolled. Patients received tislelizumab 200 mg intravenously every 3 weeks. Objective response rate (ORR; primary endpoint), duration of response (DoR), and progression-free survival (PFS) were assessed by independent review committee (Response Evaluation Criteria in Solid Tumors v1.1).

Results: Eighty patients were enrolled and treated; 75 (93.8%) patients had measurable disease at baseline. Most had metastatic disease and received at least one prior therapy for advanced/metastatic disease (n=79; 98.8%). At primary analysis (data cutoff July 8, 2021; median follow-up 15.2 months), overall ORR [46.7%; 95% confidence interval (95% CI), 35.1-58.6; one-sided P<0.0001] and ORR across tumor-specific subgroups [colorectal (n=46): 39.1% (95% CI, 25.1-54.6); gastric/gastroesophageal junction (n=9): 55.6% (95% CI, 21.2-86.3); others (n=20): 60.0% (95% CI, 36.1-80.9)] were significantly greater with tislelizumab vs. a prespecified historical control ORR of 10%; five (6.7%) patients had complete responses. Median DoR, PFS, and overall survival were not reached with long-term follow-up (data cutoff December 5, 2022; median follow-up 28.9 months). Tislelizumab was well tolerated with no unexpected safety signals. Treatment-related adverse events (TRAEs) of grade ≥3 occurred in 53.8% of patients; 7.5% of patients discontinued treatment due to TRAEs.

Conclusions: Tislelizumab demonstrated a significant ORR improvement in patients with previously treated, locally advanced unresectable or metastatic MSI-H/dMMR tumors and was generally well tolerated.

研究目的开放标签的II期RATIONALE-209研究评估了tislelizumab(抗程序性细胞死亡蛋白1抗体)作为微卫星不稳定性高(MSI-H)/错配修复缺陷(dMMR)肿瘤的组织诊断单药疗法:方法:研究人员招募了曾接受过治疗、局部晚期不可切除或转移性MSI-H/dMMR实体瘤的成人患者。患者每3周接受一次200毫克的tislelizumab静脉注射。客观反应率(ORR;主要终点)、反应持续时间(DoR)和无进展生存期(PFS)由独立审查委员会(实体瘤反应评估标准 v1.1)进行评估:80名患者入组并接受了治疗;75名患者(93.8%)在基线时患有可测量的疾病。大多数患者患有转移性疾病,并且之前至少接受过一次晚期/转移性疾病治疗(79 例;98.8%)。在主要分析中(数据截止日期为 2021 年 7 月 8 日;中位随访 15.2 个月),总体 ORR [46.7%;95% 置信区间 (95%CI),35.1-58.6;单侧 Pvs.预设历史对照 ORR 为 10%;5 名(6.7%)患者完全应答。长期随访未达到中位DoR、PFS和总生存期(数据截止日期为2022年12月5日;中位随访28.9个月)。Tislelizumab的耐受性良好,没有出现意外的安全信号。53.8%的患者发生了≥3级的治疗相关不良事件(TRAEs);7.5%的患者因TRAEs而中断治疗:结论:Tislelizumab可显著改善既往接受过治疗的局部晚期不可切除或转移性MSI-H/dMMR肿瘤患者的ORR,且耐受性普遍良好。
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引用次数: 0
Nucleotide excision repair gene polymorphisms and hepatoblastoma susceptibility in Eastern Chinese children: A five-center case-control study. 核苷酸切除修复基因多态性与华东地区儿童肝母细胞瘤的易感性:五中心病例对照研究
IF 7 2区 医学 Q1 ONCOLOGY Pub Date : 2024-06-30 DOI: 10.21147/j.issn.1000-9604.2024.03.06
Huimin Yin, Xianqiang Wang, Shouhua Zhang, Shaohua He, Wenli Zhang, Hongting Lu, Yizhen Wang, Jing He, Chunlei Zhou

Objective: Nucleotide excision repair (NER) plays a vital role in maintaining genome stability, and the effect of NER gene polymorphisms on hepatoblastoma susceptibility is still under investigation. This study aimed to evaluate the relationship between NER gene polymorphisms and the risk of hepatoblastoma in Eastern Chinese Han children.

Methods: In this five-center case-control study, we enrolled 966 subjects from East China (193 hepatoblastoma patients and 773 healthy controls). The TaqMan method was used to genotype 19 single nucleotide polymorphisms (SNPs) in NER pathway genes, including ERCC1, XPA, XPC, XPD, XPF, and XPG. Then, multivariate logistic regression analysis was performed, and odds ratios (ORs) and 95% confidence intervals (95% CIs) were utilized to assess the strength of associations.

Results: Three SNPs were related to hepatoblastoma risk. XPC rs2229090 and XPD rs3810366 significantly contributed to hepatoblastoma risk according to the dominant model (adjusted OR=1.49, 95% CI=1.07-2.08, P=0.019; adjusted OR=1.66, 95% CI=1.12-2.45, P=0.012, respectively). However, XPD rs238406 conferred a significantly decreased risk of hepatoblastoma under the dominant model (adjusted OR=0.68, 95% CI=0.49-0.95; P=0.024). Stratified analysis demonstrated that these significant associations were more prominent in certain subgroups. Moreover, there was evidence of functional implications of these significant SNPs suggested by online expression quantitative trait loci (eQTLs) and splicing quantitative trait loci (sQTLs) analysis.

Conclusions: In summary, NER pathway gene polymorphisms (XPC rs2229090, XPD rs3810366, and XPD rs238406) are significantly associated with hepatoblastoma risk, and further research is required to verify these findings.

目的核苷酸切除修复(NER)在维持基因组稳定性方面发挥着重要作用,而NER基因多态性对肝母细胞瘤易感性的影响仍在研究中。本研究旨在评估华东地区汉族儿童 NER 基因多态性与肝母细胞瘤发病风险之间的关系:在这项由五个中心组成的病例对照研究中,我们从华东地区招募了 966 名受试者(193 名肝母细胞瘤患者和 773 名健康对照者)。采用TaqMan方法对ERCC1、XPA、XPC、XPD、XPF和XPG等NER通路基因中的19个单核苷酸多态性(SNPs)进行基因分型。然后进行多变量逻辑回归分析,并利用几率比(ORs)和95%置信区间(95% CIs)评估相关性的强度:结果:三个 SNP 与肝母细胞瘤风险有关。根据显性模型,XPC rs2229090和XPD rs3810366对肝母细胞瘤风险有显著影响(调整后OR=1.49,95% CI=1.07-2.08,P=0.019;调整后OR=1.66,95% CI=1.12-2.45,P=0.012)。然而,在显性模型下,XPD rs238406可显著降低肝母细胞瘤的风险(调整OR=0.68,95% CI=0.49-0.95;P=0.024)。分层分析表明,这些显著关联在某些亚组中更为突出。此外,在线表达定量性状位点(eQTLs)和剪接定量性状位点(sQTLs)分析表明,这些显著的SNPs具有功能影响:总之,NER通路基因多态性(XPC rs2229090、XPD rs3810366和XPD rs238406)与肝母细胞瘤风险显著相关,需要进一步研究来验证这些发现。
{"title":"Nucleotide excision repair gene polymorphisms and hepatoblastoma susceptibility in Eastern Chinese children: A five-center case-control study.","authors":"Huimin Yin, Xianqiang Wang, Shouhua Zhang, Shaohua He, Wenli Zhang, Hongting Lu, Yizhen Wang, Jing He, Chunlei Zhou","doi":"10.21147/j.issn.1000-9604.2024.03.06","DOIUrl":"10.21147/j.issn.1000-9604.2024.03.06","url":null,"abstract":"<p><strong>Objective: </strong>Nucleotide excision repair (NER) plays a vital role in maintaining genome stability, and the effect of NER gene polymorphisms on hepatoblastoma susceptibility is still under investigation. This study aimed to evaluate the relationship between NER gene polymorphisms and the risk of hepatoblastoma in Eastern Chinese Han children.</p><p><strong>Methods: </strong>In this five-center case-control study, we enrolled 966 subjects from East China (193 hepatoblastoma patients and 773 healthy controls). The TaqMan method was used to genotype 19 single nucleotide polymorphisms (SNPs) in NER pathway genes, including <i>ERCC1</i>, <i>XPA</i>, <i>XPC</i>, <i>XPD</i>, <i>XPF</i>, and <i>XPG</i>. Then, multivariate logistic regression analysis was performed, and odds ratios (ORs) and 95% confidence intervals (95% CIs) were utilized to assess the strength of associations.</p><p><strong>Results: </strong>Three SNPs were related to hepatoblastoma risk. <i>XPC</i> rs2229090 and <i>XPD</i> rs3810366 significantly contributed to hepatoblastoma risk according to the dominant model (adjusted OR=1.49, 95% CI=1.07-2.08, P=0.019; adjusted OR=1.66, 95% CI=1.12-2.45, P=0.012, respectively). However, <i>XPD</i> rs238406 conferred a significantly decreased risk of hepatoblastoma under the dominant model (adjusted OR=0.68, 95% CI=0.49-0.95; P=0.024). Stratified analysis demonstrated that these significant associations were more prominent in certain subgroups. Moreover, there was evidence of functional implications of these significant SNPs suggested by online expression quantitative trait loci (eQTLs) and splicing quantitative trait loci (sQTLs) analysis.</p><p><strong>Conclusions: </strong>In summary, NER pathway gene polymorphisms (<i>XPC</i> rs2229090, <i>XPD</i> rs3810366, and <i>XPD</i> rs238406) are significantly associated with hepatoblastoma risk, and further research is required to verify these findings.</p>","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":null,"pages":null},"PeriodicalIF":7.0,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11230887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141582008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Effectiveness and safety of combined nimotuzumab and S-1 chemotherapy with concurrent radiotherapy for locally advanced esophageal cancer in malnourished and elderly patients: A prospective phase II study. 尼莫妥珠单抗和 S-1 化疗联合放疗治疗营养不良和老年局部晚期食管癌的有效性和安全性:前瞻性II期研究。
IF 7 2区 医学 Q1 ONCOLOGY Pub Date : 2024-06-30 DOI: 10.21147/j.issn.1000-9604.2024.03.04
Guojie Feng, Jiao Li, Nuo Yu, Ziyu Zheng, Xiongtao Yang, Lei Deng, Tao Zhang, Wenqing Wang, Wenyang Liu, Jianyang Wang, Qinfu Feng, Jima Lyu, Zefen Xiao, Zongmei Zhou, Nan Bi, Jianjun Qin, Xin Wang

Objective: Definitive chemoradiotherapy (dCRT) is the standard treatment for unresectable locally advanced esophageal cancer. However, this treatment is associated with substantial toxicity, and most malnourished or elderly patients are unable to complete this therapy. Therefore, there is a need for a more suitable radiotherapy combination regimen for this population. This study was aimed to evaluate the efficacy and safety of a combination regimen comprising chemotherapy with nimotuzumab and S-1 and concurrent radiotherapy for patients with fragile locally advanced esophageal cancer with a high Nutritional Risk Screening 2002 (NRS-2002) score.

Methods: Eligible patients with unresectable esophageal carcinoma who had an NRS-2002 score of 2 or higher were enrolled. They were treated with S-1 and nimotuzumab with concurrent radiotherapy, followed by surgery or definitive radiotherapy. The primary endpoint was the locoregional control (LRC) rate.

Results: A total of 55 patients who met the study criteria were enrolled. After completion of treatment, surgery was performed in 15 patients and radiotherapy was continued in 40 patients. The median follow-up period was 33.3 [95% confidence interval (95% CI), 31.4-35.1)] months. The LRC rate was 77.2% (95% CI, 66.6%-89.4%) at 1 year in the entire population. The overall survival (OS) rate and event-free survival (EFS) rate were 57.5% and 51.5% at 3 years, respectively. Surgery was associated with better LRC [hazard ratio (HR)=0.16; 95% CI, 0.04-0.70; P=0.015], OS (HR=0.19; 95% CI, 0.04-0.80; P=0.024), and EFS (HR=0.25; 95% CI, 0.08-0.75; P=0.013). Most adverse events were of grade 1 or 2, and no severe adverse events occurred.

Conclusions: For malnourished or elderly patients with locally advanced esophageal cancer, radiotherapy combined with nimotuzumab and S-1 is effective and has a good safety profile.

目的:确定性化放疗(dCRT)是治疗无法切除的局部晚期食管癌的标准疗法。然而,这种治疗方法有很大的毒性,而且大多数营养不良或老年患者无法完成这种治疗。因此,需要一种更适合这一人群的放疗联合方案。本研究旨在评估尼莫妥珠单抗和S-1化疗与同期放疗联合疗法对营养风险筛查2002(NRS-2002)评分较高的脆弱局部晚期食管癌患者的疗效和安全性:入选患者均为 NRS-2002 评分为 2 分或以上的不可切除食管癌患者。他们在接受 S-1 和尼莫妥珠单抗治疗的同时接受放疗,然后进行手术或最终放疗。主要终点是局部控制率(LRC):共有55名符合研究标准的患者入组。治疗结束后,15 名患者接受了手术治疗,40 名患者继续接受放疗。中位随访时间为 33.3 [95% 置信区间(95% CI),31.4-35.1]个月。全部患者一年后的LRC率为77.2%(95% CI,66.6%-89.4%)。3年后的总生存率(OS)和无事件生存率(EFS)分别为57.5%和51.5%。手术与更好的LRC[危险比(HR)=0.16;95% CI,0.04-0.70;P=0.015]、OS(HR=0.19;95% CI,0.04-0.80;P=0.024)和EFS(HR=0.25;95% CI,0.08-0.75;P=0.013)相关。大多数不良反应为1级或2级,未发生严重不良反应:结论:对于营养不良或高龄的局部晚期食管癌患者,放疗联合尼莫妥珠单抗和S-1是有效的,并且具有良好的安全性。
{"title":"Effectiveness and safety of combined nimotuzumab and S-1 chemotherapy with concurrent radiotherapy for locally advanced esophageal cancer in malnourished and elderly patients: A prospective phase II study.","authors":"Guojie Feng, Jiao Li, Nuo Yu, Ziyu Zheng, Xiongtao Yang, Lei Deng, Tao Zhang, Wenqing Wang, Wenyang Liu, Jianyang Wang, Qinfu Feng, Jima Lyu, Zefen Xiao, Zongmei Zhou, Nan Bi, Jianjun Qin, Xin Wang","doi":"10.21147/j.issn.1000-9604.2024.03.04","DOIUrl":"10.21147/j.issn.1000-9604.2024.03.04","url":null,"abstract":"<p><strong>Objective: </strong>Definitive chemoradiotherapy (dCRT) is the standard treatment for unresectable locally advanced esophageal cancer. However, this treatment is associated with substantial toxicity, and most malnourished or elderly patients are unable to complete this therapy. Therefore, there is a need for a more suitable radiotherapy combination regimen for this population. This study was aimed to evaluate the efficacy and safety of a combination regimen comprising chemotherapy with nimotuzumab and S-1 and concurrent radiotherapy for patients with fragile locally advanced esophageal cancer with a high Nutritional Risk Screening 2002 (NRS-2002) score.</p><p><strong>Methods: </strong>Eligible patients with unresectable esophageal carcinoma who had an NRS-2002 score of 2 or higher were enrolled. They were treated with S-1 and nimotuzumab with concurrent radiotherapy, followed by surgery or definitive radiotherapy. The primary endpoint was the locoregional control (LRC) rate.</p><p><strong>Results: </strong>A total of 55 patients who met the study criteria were enrolled. After completion of treatment, surgery was performed in 15 patients and radiotherapy was continued in 40 patients. The median follow-up period was 33.3 [95% confidence interval (95% CI), 31.4-35.1)] months. The LRC rate was 77.2% (95% CI, 66.6%-89.4%) at 1 year in the entire population. The overall survival (OS) rate and event-free survival (EFS) rate were 57.5% and 51.5% at 3 years, respectively. Surgery was associated with better LRC [hazard ratio (HR)=0.16; 95% CI, 0.04-0.70; P=0.015], OS (HR=0.19; 95% CI, 0.04-0.80; P=0.024), and EFS (HR=0.25; 95% CI, 0.08-0.75; P=0.013). Most adverse events were of grade 1 or 2, and no severe adverse events occurred.</p><p><strong>Conclusions: </strong>For malnourished or elderly patients with locally advanced esophageal cancer, radiotherapy combined with nimotuzumab and S-1 is effective and has a good safety profile.</p>","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":null,"pages":null},"PeriodicalIF":7.0,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11230888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141579092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Evidence-based expert consensus on clinical management of safety of Bruton's tyrosine kinase inhibitors (2024). 关于布鲁顿酪氨酸激酶抑制剂安全性临床管理的循证专家共识(2024 年)。
IF 7 2区 医学 Q1 ONCOLOGY Pub Date : 2024-06-30 DOI: 10.21147/j.issn.1000-9604.2024.03.02
Zaiwei Song, Dan Jiang, Lingling Yu, Yixuan Chen, Daobin Zhou, Yue Li, Depei Wu, Lingli Zhang, Liyan Miao, Jun Ma, Jun Zhu, Hongmei Jing, Rongsheng Zhao, On Behalf Of The Steering Committee, The Consensus Panel And The Evidence Synthesis Group Evidence-Based Pharmacy Professional Committee Of Chinese Pharmaceutical Association Cpa, Hospital Pharmacy Professional Committee Of Chinese Pharmaceutical Association Cpa, Division Of Therapeutic Drug Monitoring Of Chinese Pharmacological Society Cps, Expert Committee On Lymphoma Of Chinese Society Of Clinical Oncology Csco, Expert Committee On Leukemia Of Chinese Society Of Clinical Oncology Csco, Society Of Integrative Cardio-Oncology Of China Anti-Cancer Association Caca, Chinese Society Of Hematology Of Chinese Medical Association Cma, Hospital Pharmacy Professional Committee Of Cross-Straits Medicine Exchange Association Smea

Bruton's tyrosine kinase inhibitors (BTKis) have revolutionized the treatment of B-cell lymphomas. However, safety issues related to the use of BTKis may hinder treatment continuity and further affect clinical efficacy. A comprehensive and systematic expert consensus from a pharmacological perspective is lacking for safety issues associated with BTKi treatment. A multidisciplinary consensus working group was established, comprising 35 members from the fields of hematology, cardiovascular disease, cardio-oncology, clinical pharmacy, and evidence-based medicine. This evidence-based expert consensus was formulated using an evidence-based approach and the Delphi method. The Joanna Briggs Institute Critical Appraisal (JBI) tool and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach were used to rate the quality of evidence and grade the strength of recommendations, respectively. This consensus provides practical recommendations for BTKis medication based on nine aspects within three domains, including the management of common adverse drug events such as bleeding, cardiovascular events, and hematological toxicity, as well as the management of drug-drug interactions and guidance for special populations. This multidisciplinary expert consensus could contribute to promoting a multi-dimensional, comprehensive and standardized management of BTKis.

布鲁顿酪氨酸激酶抑制剂(BTKis)彻底改变了B细胞淋巴瘤的治疗方法。然而,与使用 BTKis 相关的安全性问题可能会阻碍治疗的持续性,并进一步影响临床疗效。目前还缺乏从药理学角度对与 BTKi 治疗相关的安全性问题达成全面、系统的专家共识。我们成立了一个多学科共识工作组,由来自血液学、心血管疾病、心肿瘤学、临床药学和循证医学领域的 35 名成员组成。该循证专家共识是采用循证方法和德尔菲法达成的。乔安娜-布里格斯研究所(Joanna Briggs Institute)的批判性评估(JBI)工具和建议评估、发展和评价分级(GRADE)方法分别用于评价证据的质量和建议的强度。该共识从三个领域的九个方面为 BTKis 药物治疗提供了实用建议,包括出血、心血管事件和血液毒性等常见药物不良事件的处理,以及药物间相互作用的处理和特殊人群的指导。这一多学科专家共识有助于促进对 BTKis 的多维、全面和标准化管理。
{"title":"Evidence-based expert consensus on clinical management of safety of Bruton's tyrosine kinase inhibitors (2024).","authors":"Zaiwei Song, Dan Jiang, Lingling Yu, Yixuan Chen, Daobin Zhou, Yue Li, Depei Wu, Lingli Zhang, Liyan Miao, Jun Ma, Jun Zhu, Hongmei Jing, Rongsheng Zhao, On Behalf Of The Steering Committee, The Consensus Panel And The Evidence Synthesis Group Evidence-Based Pharmacy Professional Committee Of Chinese Pharmaceutical Association Cpa, Hospital Pharmacy Professional Committee Of Chinese Pharmaceutical Association Cpa, Division Of Therapeutic Drug Monitoring Of Chinese Pharmacological Society Cps, Expert Committee On Lymphoma Of Chinese Society Of Clinical Oncology Csco, Expert Committee On Leukemia Of Chinese Society Of Clinical Oncology Csco, Society Of Integrative Cardio-Oncology Of China Anti-Cancer Association Caca, Chinese Society Of Hematology Of Chinese Medical Association Cma, Hospital Pharmacy Professional Committee Of Cross-Straits Medicine Exchange Association Smea","doi":"10.21147/j.issn.1000-9604.2024.03.02","DOIUrl":"10.21147/j.issn.1000-9604.2024.03.02","url":null,"abstract":"<p><p>Bruton's tyrosine kinase inhibitors (BTKis) have revolutionized the treatment of B-cell lymphomas. However, safety issues related to the use of BTKis may hinder treatment continuity and further affect clinical efficacy. A comprehensive and systematic expert consensus from a pharmacological perspective is lacking for safety issues associated with BTKi treatment. A multidisciplinary consensus working group was established, comprising 35 members from the fields of hematology, cardiovascular disease, cardio-oncology, clinical pharmacy, and evidence-based medicine. This evidence-based expert consensus was formulated using an evidence-based approach and the Delphi method. The Joanna Briggs Institute Critical Appraisal (JBI) tool and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach were used to rate the quality of evidence and grade the strength of recommendations, respectively. This consensus provides practical recommendations for BTKis medication based on nine aspects within three domains, including the management of common adverse drug events such as bleeding, cardiovascular events, and hematological toxicity, as well as the management of drug-drug interactions and guidance for special populations. This multidisciplinary expert consensus could contribute to promoting a multi-dimensional, comprehensive and standardized management of BTKis.</p>","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":null,"pages":null},"PeriodicalIF":7.0,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11230885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141579093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Efficacy and safety of low-dose cyclophosphamide combined with lenvatinib, pembrolizumab and TACE for unresectable hepatocellular carcinoma: A single-center, prospective, single-arm clinical trial. 小剂量环磷酰胺联合来伐替尼、pembrolizumab和TACE治疗不可切除肝细胞癌的有效性和安全性:一项单中心、前瞻性、单臂临床试验。
IF 5.1 2区 医学 Pub Date : 2024-04-30 DOI: 10.21147/j.issn.1000-9604.2024.02.02
Yupeng Ren, Yuxuan Li, Mingbo Cao, Yongchang Tang, Feng Yuan, Gaoyuan Yang, Zhiwei He, Zheng Shi, Xiaorui Su, Zhicheng Yao, Meihai Deng

Objective: Unresectable hepatocellular carcinoma (uHCC) continues to pose effective treatment options. The objective of this study was to assess the efficacy and safety of combining low-dose cyclophosphamide with lenvatinib, pembrolizumab and transarterial chemoembolization (TACE) for the treatment of uHCC.

Methods: From February 2022 to November 2023, a total of 40 patients diagnosed with uHCC were enrolled in this small-dose, single-center, single-arm, prospective study. They received a combined treatment of low-dose cyclophosphamide with lenvatinib, pembrolizumab, and TACE. Study endpoints included progression-free survival (PFS), objective response rate (ORR), and safety assessment. Tumor response was assessed using the modified Response Evaluation Criteria in Solid Tumors (mRECIST), while survival analysis was conducted through Kaplan-Meier curve analysis for overall survival (OS) and PFS. Adverse events (AEs) were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0).

Results: A total of 34 patients were included in the study. The median follow-up duration was 11.2 [95% confidence interval (95% CI), 5.3-14.6] months, and the median PFS (mPFS) was 15.5 (95% CI, 5.4-NA) months. Median OS (mOS) was not attained during the study period. The ORR was 55.9%, and the disease control rate (DCR) was 70.6%. AEs were reported in 27 (79.4%) patients. The most frequently reported AEs (with an incidence rate >10%) included abnormal liver function (52.9%), abdominal pain (44.1%), abdominal distension and constipation (29.4%), hypertension (20.6%), leukopenia (17.6%), constipation (17.6%), ascites (14.7%), and insomnia (14.7%). Abnormal liver function (14.7%) had the most common grade 3 or higher AEs.

Conclusions: A combination of low-dose cyclophosphamide with lenvatinib, pembrolizumab, and TACE is safe and effective for uHCC, showcasing a promising therapeutic strategy for managing uHCC.

目的:无法切除的肝细胞癌(uHCC)仍然是有效的治疗方案。本研究旨在评估低剂量环磷酰胺联合来伐替尼、pembrolizumab和经动脉化疗栓塞(TACE)治疗uHCC的有效性和安全性:从2022年2月到2023年11月,共有40名确诊为uHCC的患者参与了这项小剂量、单中心、单臂、前瞻性研究。他们接受了小剂量环磷酰胺联合来伐替尼、pembrolizumab和TACE的综合治疗。研究终点包括无进展生存期(PFS)、客观反应率(ORR)和安全性评估。肿瘤反应采用改良的实体瘤反应评估标准(mRECIST)进行评估,总生存期(OS)和PFS的生存分析采用卡普兰-梅耶曲线分析法。不良事件(AEs)根据美国国立癌症研究所不良事件通用术语标准(5.0版)进行评估:研究共纳入了 34 名患者。中位随访时间为11.2个月[95%置信区间(95% CI),5.3-14.6],中位PFS(mPFS)为15.5个月(95% CI,5.4-NA)。研究期间未达到中位OS(mOS)。ORR为55.9%,疾病控制率(DCR)为70.6%。27例(79.4%)患者出现了不良反应。最常报告的不良反应(发生率>10%)包括肝功能异常(52.9%)、腹痛(44.1%)、腹胀和便秘(29.4%)、高血压(20.6%)、白细胞减少(17.6%)、便秘(17.6%)、腹水(14.7%)和失眠(14.7%)。肝功能异常(14.7%)是最常见的3级或以上AEs:结论:小剂量环磷酰胺联合来伐替尼、pembrolizumab和TACE治疗uHCC安全有效,是治疗uHCC的一种有前途的治疗策略。
{"title":"Efficacy and safety of low-dose cyclophosphamide combined with lenvatinib, pembrolizumab and TACE for unresectable hepatocellular carcinoma: A single-center, prospective, single-arm clinical trial.","authors":"Yupeng Ren, Yuxuan Li, Mingbo Cao, Yongchang Tang, Feng Yuan, Gaoyuan Yang, Zhiwei He, Zheng Shi, Xiaorui Su, Zhicheng Yao, Meihai Deng","doi":"10.21147/j.issn.1000-9604.2024.02.02","DOIUrl":"10.21147/j.issn.1000-9604.2024.02.02","url":null,"abstract":"<p><strong>Objective: </strong>Unresectable hepatocellular carcinoma (uHCC) continues to pose effective treatment options. The objective of this study was to assess the efficacy and safety of combining low-dose cyclophosphamide with lenvatinib, pembrolizumab and transarterial chemoembolization (TACE) for the treatment of uHCC.</p><p><strong>Methods: </strong>From February 2022 to November 2023, a total of 40 patients diagnosed with uHCC were enrolled in this small-dose, single-center, single-arm, prospective study. They received a combined treatment of low-dose cyclophosphamide with lenvatinib, pembrolizumab, and TACE. Study endpoints included progression-free survival (PFS), objective response rate (ORR), and safety assessment. Tumor response was assessed using the modified Response Evaluation Criteria in Solid Tumors (mRECIST), while survival analysis was conducted through Kaplan-Meier curve analysis for overall survival (OS) and PFS. Adverse events (AEs) were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0).</p><p><strong>Results: </strong>A total of 34 patients were included in the study. The median follow-up duration was 11.2 [95% confidence interval (95% CI), 5.3-14.6] months, and the median PFS (mPFS) was 15.5 (95% CI, 5.4-NA) months. Median OS (mOS) was not attained during the study period. The ORR was 55.9%, and the disease control rate (DCR) was 70.6%. AEs were reported in 27 (79.4%) patients. The most frequently reported AEs (with an incidence rate >10%) included abnormal liver function (52.9%), abdominal pain (44.1%), abdominal distension and constipation (29.4%), hypertension (20.6%), leukopenia (17.6%), constipation (17.6%), ascites (14.7%), and insomnia (14.7%). Abnormal liver function (14.7%) had the most common grade 3 or higher AEs.</p><p><strong>Conclusions: </strong>A combination of low-dose cyclophosphamide with lenvatinib, pembrolizumab, and TACE is safe and effective for uHCC, showcasing a promising therapeutic strategy for managing uHCC.</p>","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11090797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140944148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
IMpower210: A phase III study of second-line atezolizumab vs. docetaxel in East Asian patients with non-small cell lung cancer. IMpower210:东亚非小细胞肺癌患者二线治疗atezolizumab与多西他赛的III期研究。
IF 5.1 2区 医学 Pub Date : 2024-04-30 DOI: 10.21147/j.issn.1000-9604.2024.02.01
Yi-Long Wu, Shun Lu, Gongyan Chen, Jianxing He, Jifeng Feng, Yiping Zhang, Liyan Jiang, Hongming Pan, Jianhua Chang, Jian Fang, Amy Cai, Lilian Bu, Jane Shi, Jinjing Xia

Objective: IMpower210 (NCT02813785) explored the efficacy and safety of single-agent atezolizumab vs. docetaxel as second-line treatment for advanced non-small cell lung cancer (NSCLC) in East Asian patients.

Methods: Key eligibility criteria for this phase III, open-label, randomized study included age ≥18 years; histologically documented advanced NSCLC per the Union for International Cancer Control/American Joint Committee on Cancer staging system (7th edition); Eastern Cooperative Oncology Group performance status of 0 or 1; and disease progression following platinum-based chemotherapy for advanced or metastatic NSCLC. Patients were randomized 2:1 to receive either atezolizumab (1,200 mg) or docetaxel (75 mg/m2). The primary study endpoint was overall survival (OS) in the intention-to-treat (ITT) population with wild-type epidermal growth factor receptor expression (ITT EGFR-WT) and in the overall ITT population.

Results: Median OS in the ITT EGFR-WT population (n=467) was 12.3 [95% confidence interval (95% CI), 10.3-13.8] months in the atezolizumab arm (n=312) and 9.9 (95% CI, 7.8-13.9) months in the docetaxel arm [n=155; stratified hazard ratio (HR), 0.82; 95% CI, 0.66-1.03]. Median OS in the overall ITT population was 12.5 (95% CI, 10.8-13.8) months with atezolizumab treatment and 11.1 (95% CI, 8.4-14.2) months (n=377) with docetaxel treatment (n=188; stratified HR, 0.87; 95% CI, 0.71-1.08). Grade 3/4 treatment-related adverse events (TRAEs) occurred in 18.4% of patients in the atezolizumab arm and 50.0% of patients in the docetaxel arm.

Conclusions: IMpower210 did not meet its primary efficacy endpoint of OS in the ITT EGFR-WT or overall ITT populations. Atezolizumab was comparatively more tolerable than docetaxel, with a lower incidence of grade 3/4 TRAEs.

研究目的IMpower210(NCT02813785)探讨了单药阿特珠单抗与多西他赛作为东亚患者晚期非小细胞肺癌(NSCLC)二线治疗的有效性和安全性:这项III期开放标签随机研究的主要资格标准包括:年龄≥18岁;根据国际癌症控制联盟/美国癌症联合委员会分期系统(第7版),有组织学记录的晚期NSCLC;东部合作肿瘤学组表现状态为0或1;晚期或转移性NSCLC铂类化疗后疾病进展。患者以2:1的比例随机接受阿特珠单抗(1200毫克)或多西他赛(75毫克/平方米)治疗。主要研究终点是野生型表皮生长因子受体表达(ITT EGFR-WT)的意向治疗(ITT)人群和总体ITT人群的总生存期(OS):ITT EGFR-WT人群(n=467)中,阿特珠单抗治疗组(n=312)的中位OS为12.3个月[95%置信区间(95% CI),10.3-13.8],多西他赛治疗组为9.9个月(95% CI,7.8-13.9)[n=155;分层危险比(HR),0.82;95% CI,0.66-1.03]。在ITT人群中,阿特珠单抗治疗的中位OS为12.5个月(95% CI,10.8-13.8个月),多西他赛治疗的中位OS为11.1个月(95% CI,8.4-14.2个月)(n=377)(n=188;分层HR,0.87;95% CI,0.71-1.08)。阿特珠单抗治疗组18.4%的患者和多西他赛治疗组50.0%的患者发生了3/4级治疗相关不良事件(TRAEs):IMpower210在ITT表皮生长因子受体-WT或总体ITT人群中未达到OS的主要疗效终点。与多西他赛相比,Atezolizumab的耐受性更好,3/4级TRAE发生率更低。
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引用次数: 0
New insights into mechanisms and interventions of locoregional therapies for hepatocellular carcinoma. 对肝细胞癌局部治疗机制和干预措施的新认识。
IF 5.1 2区 医学 Pub Date : 2024-04-30 DOI: 10.21147/j.issn.1000-9604.2024.02.06
Hanyuan Liu, Chunmei Wang, Ruiqiang Wang, Hengsong Cao, Yongfang Cao, Tian Huang, Zhengqing Lu, Hua Xiao, Mengcheng Hu, Hanjin Wang, Jun Zhao

Hepatocellular carcinoma (HCC) is responsible for a significant number of cancer-related deaths worldwide and its incidence is increasing. Locoregional treatments, which are precision procedures guided by imaging to specifically target liver tumors, play a critical role in the management of a substantial portion of HCC cases. These therapies have become an essential element of the HCC treatment landscape, with transarterial chemoembolization (TACE) being the treatment of choice for patients with intermediate to advanced stages of the disease. Other locoregional therapies, like radiofrequency ablation, are highly effective for small, early-stage HCC. Nevertheless, the advent of targeted immunotherapy has challenged these established treatments. Tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) have shown remarkable efficacy in clinical settings. However, their specific uses and the development of resistance in subsequent treatments have led clinicians to reevaluate the future direction of HCC therapy. This review concentrates on the distinct features of both systemic and novel locoregional therapies. We investigate their effects on the tumor microenvironment at the molecular level and discuss how targeted immunotherapy can be effectively integrated with locoregional therapies. We also examine research findings from retrospective studies and randomized controlled trials on various combined treatment regimens, assessing their validity to determine the future evolution of locoregional therapies within the framework of personalized, comprehensive treatment.

肝细胞癌(HCC)是造成全球大量癌症相关死亡的原因,而且其发病率还在不断上升。局部治疗是一种通过成像引导、专门针对肝脏肿瘤的精确手术,在相当一部分 HCC 病例的治疗中发挥着至关重要的作用。经动脉化疗栓塞术(TACE)是中晚期患者的首选治疗方法。其他局部疗法,如射频消融术,对早期小规模的 HCC 非常有效。然而,靶向免疫疗法的出现对这些既有疗法提出了挑战。酪氨酸激酶抑制剂(TKIs)和免疫检查点抑制剂(ICIs)已在临床中显示出显著疗效。然而,这些药物的特殊用途以及后续治疗中耐药性的产生促使临床医生重新评估 HCC 治疗的未来方向。本综述将集中讨论全身性疗法和新型局部疗法的不同特点。我们研究了它们在分子水平上对肿瘤微环境的影响,并讨论了靶向免疫疗法如何与局部治疗有效结合。我们还考察了各种联合治疗方案的回顾性研究和随机对照试验的研究成果,评估其有效性,以确定局部区域疗法在个性化综合治疗框架内的未来发展。
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引用次数: 0
Circulating tumor DNA and its role in detection, prognosis and therapeutics of hepatocellular carcinoma. 循环肿瘤 DNA 及其在肝细胞癌的检测、预后和治疗中的作用。
IF 5.1 2区 医学 Pub Date : 2024-04-30 DOI: 10.21147/j.issn.1000-9604.2024.02.07
Sana Rashid, Yingchuan Sun, Umair Ali Khan Saddozai, Sikandar Hayyat, Muhammad Usman Munir, Muhammad Usman Akbar, Muhammad Babar Khawar, Zhiguang Ren, Xinying Ji, Malik Ihsan Ullah Khan

Hepatocellular carcinoma (HCC) is considered the fifth most prevalent cancer among all types of cancers and has the third most morbidity value. It has the most frequent duplication time and a high recurrence rate. Recently, the most unique technique used is liquid biopsies, which carry many markers; the most prominent is circulating tumor DNA (ctDNA). Varied methods are used to investigate ctDNA, including various forms of polymerase chain reaction (PCR) [emulsion PCR (ePCR), digital PCR (dPCR), and bead, emulsion, amplification, magnetic (BEAMing) PCR]. Hence ctDNA is being recognized as a potential biomarker that permits early cancer detection, treatment monitoring, and predictive data on tumor burden are subjective to therapy or surgery. Numerous ctDNA biomarkers have been investigated based on their alterations such as 1) single nucleotide variations (either insertion or deletion of a nucleotide) markers including TP53, KRAS, and CCND1; 2) copy number variations which include markers such as CDK6, EFGR, MYC and BRAF; 3) DNA methylation (RASSF1A, SEPT9, KMT2C and CCNA2); 4) homozygous mutation includes ctDNA markers as CDKN2A, AXIN1; and 5) gain or loss of function of the genes, particularly for HCC. Various researchers have conducted many studies and gotten fruitful results. Still, there are some drawbacks to ctDNA namely low quantity, fragment heterogeneity, less stability, limited mutant copies and standards, and differential sensitivity. However, plenty of investigations demonstrate ctDNA's significance as a polyvalent biomarker for cancer and can be viewed as a future diagnostic, prognostic and therapeutic agent. This article overviews many conditions in genetic changes linked to the onset and development of HCC, such as dysregulated signaling pathways, somatic mutations, single-nucleotide polymorphisms, and genomic instability. Additionally, efforts are also made to develop treatments for HCC that are molecularly targeted and to unravel some of the genetic pathways that facilitate its early identification.

肝细胞癌(HCC)被认为是所有癌症类型中发病率排名第五的癌症,发病率排名第三。它的重复时间最长,复发率也很高。最近,最独特的技术是液体活检,液体活检携带许多标记物,其中最突出的是循环肿瘤 DNA(ctDNA)。研究ctDNA的方法多种多样,包括各种形式的聚合酶链反应(PCR)[乳液 PCR(ePCR)、数字 PCR(dPCR)和磁珠、乳液、扩增、磁性(BEAMing)PCR]。因此,ctDNA 被认为是一种潜在的生物标记物,可用于早期癌症检测、治疗监测以及肿瘤负荷的预测数据,对治疗或手术具有主观性。目前已根据ctDNA的变化研究了许多ctDNA生物标志物,如:1)单核苷酸变异(核苷酸的插入或缺失)标志物,包括TP53、KRAS和CCND1;2)拷贝数变异,包括 CDK6、EFGR、MYC 和 BRAF 等标记物;3)DNA 甲基化(RASSF1A、SEPT9、KMT2C 和 CCNA2);4)同基因突变,包括 CDKN2A、AXIN1 等 ctDNA 标记物;以及 5)基因的功能获得或丧失,尤其是对 HCC 而言。不同的研究人员进行了大量的研究,并取得了丰硕的成果。不过,ctDNA 也存在一些缺点,如数量少、片段异质性、稳定性差、突变拷贝和标准有限以及敏感性不同。不过,大量研究表明,ctDNA 是一种多价的癌症生物标记物,可被视为未来的诊断、预后和治疗药物。本文概述了与 HCC 发病和发展相关的许多基因变化情况,如信号通路失调、体细胞突变、单核苷酸多态性和基因组不稳定性。此外,该研究还致力于开发针对 HCC 的分子靶向治疗方法,并揭示一些有助于早期识别 HCC 的遗传途径。
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引用次数: 0
期刊
Chinese Journal of Cancer Research
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