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Combination therapy using low-dose anlotinib and immune checkpoint inhibitors for extensive-stage small cell lung cancer 使用小剂量安罗替尼和免疫检查点抑制剂联合治疗广泛期小细胞肺癌。
Pub Date : 2024-10-28 DOI: 10.1002/cai2.155
Han Li, Shumin Yuan, Han Wu, Yajie Wang, Yichen Ma, Xiance Tang, Xiaomin Fu, Lingdi Zhao, Benling Xu, Tiepeng Li, Peng Qin, Hongqin You, Lu Han, Zibing Wang

Background

This study evaluated the efficacy and safety of low-dose anlotinib combined with immune checkpoint inhibitors as second-line or later treatment for extensive-stage small cell lung cancer (ES-SCLC).

Methods

The study included 42 patients with ES-SCLC who were treated with low-dose anlotinib combined with programmed cell death protein 1/programmed cell death-ligand 1 inhibitors at Henan Cancer Hospital between March 2019 and August 2022. We retrospectively analyzed the efficacy and safety data for these patients. Indicators assessed included progression-free survival (PFS), overall survival (OS), the overall response rate (ORR), the disease control rate (DCR), and adverse events (AEs). Prognostic factors were identified in univariate and multivariate analyses.

Results

Median PFS was 11.0 months (95% CI: 7.868–14.132) and median OS was 17.3 months (95% CI: 11.517–23.083). The ORR was 28.5% and the DCR was 95.2%. Treatment-related AEs were noted in 27 patients (64.3%), the most common of which was thyroid dysfunction (26.2%). Grade 3/4 treatment-related AEs were observed in two patients (4.8%).

Conclusions

A combination of low-dose anlotinib and immune checkpoint inhibitors as second-line or later treatment for ES-SCLC may achieve longer PFS and OS and have manageable AEs.

研究背景本研究评估了小剂量安罗替尼联合免疫检查点抑制剂作为广泛期小细胞肺癌(ES-SCLC)二线或后期治疗的有效性和安全性:研究纳入了2019年3月至2022年8月在河南省肿瘤医院接受低剂量安罗替尼联合程序性细胞死亡蛋白1/程序性细胞死亡配体1抑制剂治疗的42例ES-SCLC患者。我们对这些患者的疗效和安全性数据进行了回顾性分析。评估指标包括无进展生存期(PFS)、总生存期(OS)、总反应率(ORR)、疾病控制率(DCR)和不良事件(AEs)。单变量和多变量分析确定了预后因素:中位 PFS 为 11.0 个月(95% CI:7.868-14.132),中位 OS 为 17.3 个月(95% CI:11.517-23.083)。ORR为28.5%,DCR为95.2%。27名患者(64.3%)出现了治疗相关的AEs,其中最常见的是甲状腺功能障碍(26.2%)。2名患者(4.8%)出现了3/4级治疗相关不良反应:结论:小剂量安罗替尼和免疫检查点抑制剂联合作为ES-SCLC的二线或后期治疗,可获得更长的PFS和OS,且AEs可控。
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引用次数: 0
Beyond clinical trials: CDK4/6 inhibitor efficacy predictors and nomogram model from real-world evidence in metastatic breast cancer 超越临床试验:CDK4/6抑制剂疗效预测指标和来自转移性乳腺癌真实世界证据的提名图模型。
Pub Date : 2024-10-25 DOI: 10.1002/cai2.143
Binliang Liu, Zhe-Yu Hu, Ning Xie, Liping Liu, Jing Li, Xiaohong Yang, Huawu Xiao, Xuran Zhao, Can Tian, Hui Wu, Jun Lu, Jianxiang Gao, Xuming Hu, Min Cao, Zhengrong Shui, Yu Tang, Quchang Ouyang

Background

CDK4/6 inhibitors (CDK4/6i) have shown promising results in the treatment of hormone receptor-positive (HR+) metastatic breast cancer (MBC) when combined with endocrine therapy (ET). It is crucial to evaluate the actual effectiveness and safety of CDK4/6i in clinical practice, as well as to analyze the factors that can predict their outcomes.

Methods

Patients with HR+ MBC who received CDK4/6i-based therapy between May 2016 and May 2023 at Hunan Cancer Hospital were evaluated for progression-free survival (PFS). Adverse reactions were assessed based on the National Cancer Institute Common Toxicity Criteria (version 5.0).

Results

This study included 344 patients, with a median PFS (mPFS) of 12.8 months (range: 10.4–15.2 months). After adjustment, Cox multivariate regression analysis revealed that visceral metastasis (specifically liver and brain metastases), Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥ 1, estrogen receptor ≤ 80%, progesterone receptor ≤ 10%, Ki-67 > 30%, and treatment in later stages were significant factors associated with reduced PFS. Based on this, we created a prognostic nomogram and validated its performance, obtaining a C-index of 0.714 (95% confidence interval: 0.640–0.787) as well as reliable calibration and clinical impact. The mPFS of CDK4/6i rechallenge was 7.7 months; for patients who initially discontinued CDK4/6i for reasons other than disease progression, CDK4/6i rechallenge still provided a mPFS of 11.4 months. The tolerability and safety of combining CDK4/6is with ET were manageable. Adverse events led to treatment discontinuation in 3.8% of patients. Neutropenia (29.1%), leukopenia (13.7%), and anemia (4.1%) were the primary grade 3/4 adverse reactions.

Conclusions

This real-world study highlights the ample efficacy and reasonable safety of combined CDK4/6i and ET in patients with HR+ MBC. Individualized treatment decisions and ongoing safety monitoring are important to optimize the therapeutic benefit of CDK4/6i treatment.

背景:CDK4/6抑制剂(CDK4/6i)与内分泌疗法(ET)联合治疗激素受体阳性(HR+)转移性乳腺癌(MBC)已显示出良好的疗效。评估CDK4/6i在临床实践中的实际有效性和安全性以及分析预测其结果的因素至关重要:方法:对2016年5月至2023年5月期间在湖南省肿瘤医院接受CDK4/6i治疗的HR+ MBC患者进行无进展生存期(PFS)评估。不良反应根据美国国立癌症研究所通用毒性标准(5.0版)进行评估:该研究共纳入 344 名患者,中位无进展生存期(mPFS)为 12.8 个月(范围:10.4-15.2 个月)。经过调整后,Cox 多变量回归分析显示,内脏转移(特别是肝脏和脑转移)、东部合作肿瘤学组表现状态(ECOG PS)≥1、雌激素受体≤80%、孕激素受体≤10%、Ki-67 > 30%以及晚期治疗是与 PFS 降低相关的重要因素。在此基础上,我们创建了一个预后提名图,并验证了其性能,获得了 0.714 的 C 指数(95% 置信区间:0.640-0.787)以及可靠的校准和临床影响。CDK4/6i再治疗的mPFS为7.7个月;对于因疾病进展以外的原因停用CDK4/6i的患者,CDK4/6i再治疗的mPFS仍为11.4个月。CDK4/6i与ET联合治疗的耐受性和安全性是可控的。3.8%的患者因不良反应而中断治疗。中性粒细胞减少(29.1%)、白细胞减少(13.7%)和贫血(4.1%)是主要的3/4级不良反应:这项真实世界研究强调了CDK4/6i和ET联合治疗HR+ MBC患者的充分疗效和合理安全性。个体化治疗决策和持续的安全性监测对于优化CDK4/6i治疗的疗效非常重要。
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引用次数: 0
Prognostic nomograms for young breast cancer: A retrospective study based on the SEER and METABRIC databases 年轻乳腺癌的预后提名图:基于 SEER 和 METABRIC 数据库的回顾性研究。
Pub Date : 2024-10-25 DOI: 10.1002/cai2.152
Yongxin Li, Xinlong Tao, Yinyin Ye, Yuyao Tang, Zhengbo Xu, Yaming Tian, Zhen Liu, Jiuda Zhao

Background

Young breast cancer (YBC) is a subset of breast cancer that is often more aggressive, but less is known about its prognosis. In this study, we aimed to generate nomograms to predict the overall survival (OS) and breast cancer-specific survival (BCSS) of YBC patients.

Methods

Data of women diagnosed with YBC between 2010 and 2020 were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. The patients were randomly allocated into a training cohort (n = 15,227) and internal validation cohort (n = 6,526) at a 7:3 ratio. With the Cox regression models, significant prognostic factors were identified and used to construct 3-, 5-, and 10-year nomograms of OS and BCSS. Data from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) database were used as an external validation cohort (n = 90).

Results

We constructed nomograms incorporating 10 prognostic factors for OS and BCSS. These nomograms demonstrated strong predictive accuracy for OS and BCSS in the training cohort, with C-indexes of 0.806 and 0.813, respectively. The calibration curves verified that the nomograms have good prediction accuracy. Decision curve analysis demonstrated their practical clinical value for predicting YBC patient survival rates. Additionally, we provided dynamic nomograms to improve the operability of the results. The risk stratification ability assessment also showed that the OS and BCSS rates of the low-risk group were significantly better than those of the high-risk group.

Conclusions

Here, we generated and validated more comprehensive and accurate OS and BCSS nomograms than models previously developed for YBC. These nomograms can help clinicians evaluate patient prognosis and make clinical decisions.

背景:年轻乳腺癌(YBC)是乳腺癌的一个亚型,通常更具侵袭性,但对其预后的了解较少。在这项研究中,我们旨在生成预测 YBC 患者总生存期(OS)和乳腺癌特异性生存期(BCSS)的提名图:方法:我们从监测、流行病学和最终结果(SEER)数据库中获取了2010年至2020年间被诊断为YBC的女性数据。患者按7:3的比例随机分配到训练队列(n=15227)和内部验证队列(n=6526)中。通过Cox回归模型,确定了重要的预后因素,并利用这些因素构建了3年、5年和10年的OS和BCSS提名图。来自国际乳腺癌分子分类联盟(METABRIC)数据库的数据被用作外部验证队列(n = 90):结果:我们构建了包含10个OS和BCSS预后因素的提名图。在训练队列中,这些提名图对OS和BCSS的预测准确性很高,C指数分别为0.806和0.813。校准曲线验证了提名图具有良好的预测准确性。决策曲线分析证明了它们在预测 YBC 患者生存率方面的实用临床价值。此外,我们还提供了动态提名图,以提高结果的可操作性。风险分层能力评估也显示,低风险组的OS和BCSS率明显优于高风险组:在此,我们生成并验证了比之前为 YBC 开发的模型更全面、更准确的 OS 和 BCSS 直方图。这些提名图可以帮助临床医生评估患者的预后并做出临床决策。
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引用次数: 0
Retinoic acid receptor responder 2 and lipid metabolic reprogramming: A new insight into brain metastasis 视黄酸受体应答器 2 与脂质代谢重编程:脑转移的新视角
Pub Date : 2024-10-24 DOI: 10.1002/cai2.148
Lulu Wang, Yan Gao

The brain is a common metastatic site for carcinoma, and metabolic reprogramming is crucial for organ-tropic metastatic formation. Li et al. found RARRES2 deficiency affected lipid metabolic reprogramming through PTEN-mTOR-SREBP1 pathway and promoted BCBrM. Other studies revealed that lipid metabolic reprogramming is part of metabolic adaptation to central nervous system. Overall, there is an intricate connection between lipid metabolism and brain metastases, and disrupting this connection may be a potential therapeutic target for BCBrM treatment.

脑部是癌症的常见转移部位,而代谢重编程对器官转移的形成至关重要。Li等人发现,RARRES2缺乏会通过PTEN-mTOR-SREBP1途径影响脂质代谢重编程,并促进BCBrM。其他研究表明,脂质代谢重编程是中枢神经系统代谢适应的一部分。总之,脂质代谢与脑转移之间存在着错综复杂的联系,破坏这种联系可能是治疗脑转移瘤的潜在治疗靶点。
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引用次数: 0
Leukocyte immunoglobulin-like receptor B4: A keystone in immune modulation and therapeutic target in cancer and beyond 白细胞免疫球蛋白样受体 B4:免疫调节的基石和癌症及其他疾病的治疗靶点。
Pub Date : 2024-10-22 DOI: 10.1002/cai2.153
Qi Liu, Yuyang Liu, Zhanyu Yang

Leukocyte immunoglobulin-like receptor B4 (LILRB4) significantly impacts immune regulation and the pathogenesis and progression of various cancers. This review discusses LILRB4's structural attributes, expression patterns in immune cells, and molecular mechanisms in modulating immune responses. We describe the influence of LILRB4 on T cells, dendritic cells, NK cells, and macrophages, and its dual role in stimulating and suppressing immune activities. The review discusses the current research on LILRB4's involvement in acute myeloid leukemia, chronic lymphocytic leukemia, and solid tumors, such as colorectal cancer, pancreatic cancer, non-small cell lung cancer, hepatocellular carcinoma, and extramedullary multiple myeloma. The review also describes LILRB4's role in autoimmune disorders, infectious diseases, and other conditions. We evaluate the recent advancements in targeting LILRB4 using monoclonal antibodies and peptide inhibitors and their therapeutic potential in cancer treatment. Together, these studies underscore the need for further research on LILRB4's interactions in the tumor microenvironment and highlight its importance as a therapeutic target in oncology and for future clinical innovations.

白细胞免疫球蛋白样受体 B4(LILRB4)对免疫调节以及各种癌症的发病和进展有重大影响。本综述讨论了 LILRB4 的结构属性、在免疫细胞中的表达模式以及调节免疫反应的分子机制。我们描述了 LILRB4 对 T 细胞、树突状细胞、NK 细胞和巨噬细胞的影响,以及它在刺激和抑制免疫活动中的双重作用。综述讨论了目前有关 LILRB4 参与急性髓性白血病、慢性淋巴细胞白血病和实体瘤(如结直肠癌、胰腺癌、非小细胞肺癌、肝细胞癌和髓外多发性骨髓瘤)的研究。综述还介绍了 LILRB4 在自身免疫性疾病、传染性疾病和其他疾病中的作用。我们评估了利用单克隆抗体和多肽抑制剂靶向 LILRB4 的最新进展及其在癌症治疗中的治疗潜力。这些研究共同强调了进一步研究 LILRB4 在肿瘤微环境中的相互作用的必要性,并突出了其作为肿瘤学治疗靶点和未来临床创新的重要性。
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引用次数: 0
Development and validation of the NCC-BC-A scale to assess patient-reported outcomes for breast cancer patients in China 开发和验证 NCC-BC-A 量表以评估中国乳腺癌患者的患者报告结果
Pub Date : 2024-10-18 DOI: 10.1002/cai2.141
Fei Ma, Xiaoyan Yan, Xiuwen Guan, Tianmou Liu, PRO-BC China Standards Committee

Background

The commonly used international patient-reported outcome scales for breast cancer were developed before the advent of multiple targeted therapies and immunotherapies, rendering them potentially insufficient for current clinical practices. Therefore, it is necessary to develop a specific patient-reported outcome scale tailored for breast cancer patients in China to optimize the management model for these patients.

Methods

A comprehensive literature search was performed in the PubMed, Embase, Wanfang, and CNKI databases to extract dimensions and items for a potential patient-reported outcome scale. The Delphi method was used to modify, add, subtract, and adjust the language of items until the experts reached a consensus on the first draft. This draft was further refined using a cognitive test and a presurvey. The optimized scale was used for a formal survey, and the items were further analyzed and screened using metrics such as the coefficient of variation, correlation coefficient, internal item consistency, factor analysis, reliability, and validity.

Results

A total of 10,954 articles were analyzed, and 237 were used to create a pool of 277 patient-reported outcome items. Through two rounds of Delphi expert consultation, the experts' authority coefficients were 0.739 and 0.826. After a cognitive test, several items were adjusted to enhance understanding. Further adjustments were made following a presurvey of 200 advanced breast cancer patients, resulting in a 38-item patient-reported outcomes scale, termed NCC-BC-A. In the national formal survey, 588 advanced breast cancer patients participated. Principal component analysis showed good consistency among the items and sufficient difference between the dimensions. The results were normally distributed with good variation. The Cronbach's α coefficient of the scale was 0.925 and the test–retest reliability was 0.9041.

Conclusion

The NCC-BC-A scale has high validity and reliability. It comprehensively considered the characteristics of systemic treatment for breast cancer, and the specific context within China. Its implementation may help clinicians to pay more attention to quality of life of breast cancer patients and to optimize the system for managing this condition.

背景 国际上常用的乳腺癌患者报告结果量表是在多种靶向治疗和免疫治疗出现之前制定的,因此可能无法满足当前临床实践的需要。因此,有必要为中国乳腺癌患者量身定制患者报告结果量表,以优化乳腺癌患者的管理模式。 方法 在PubMed、Embase、万方和CNKI数据库中进行了全面的文献检索,以提取潜在的患者报告结果量表的维度和项目。采用德尔菲法对项目进行修改、增减和语言调整,直到专家们就初稿达成共识。通过认知测试和预调查进一步完善了初稿。优化后的量表用于正式调查,并使用变异系数、相关系数、内部项目一致性、因素分析、信度和效度等指标对项目进行进一步分析和筛选。 结果 共分析了 10954 篇文章,其中 237 篇文章被用于创建 277 个患者报告结果项目库。经过两轮德尔菲专家咨询,专家的权威系数分别为 0.739 和 0.826。经过认知测试后,对几个项目进行了调整,以加深理解。在对 200 名晚期乳腺癌患者进行预调查后,又做了进一步调整,最终形成了 38 个项目的患者报告结果量表,称为 NCC-BC-A。在全国正式调查中,共有 588 名晚期乳腺癌患者参与。主成分分析表明,各项目之间具有良好的一致性,各维度之间也有足够的差异。结果呈正态分布,差异较小。量表的 Cronbach's α 系数为 0.925,重测信度为 0.9041。 结论 NCC-BC-A 量表具有较高的效度和信度。它全面考虑了乳腺癌系统治疗的特点和中国的具体情况。该量表的实施有助于临床医生更加关注乳腺癌患者的生活质量,优化乳腺癌的治疗体系。
{"title":"Development and validation of the NCC-BC-A scale to assess patient-reported outcomes for breast cancer patients in China","authors":"Fei Ma,&nbsp;Xiaoyan Yan,&nbsp;Xiuwen Guan,&nbsp;Tianmou Liu,&nbsp;PRO-BC China Standards Committee","doi":"10.1002/cai2.141","DOIUrl":"https://doi.org/10.1002/cai2.141","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The commonly used international patient-reported outcome scales for breast cancer were developed before the advent of multiple targeted therapies and immunotherapies, rendering them potentially insufficient for current clinical practices. Therefore, it is necessary to develop a specific patient-reported outcome scale tailored for breast cancer patients in China to optimize the management model for these patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A comprehensive literature search was performed in the PubMed, Embase, Wanfang, and CNKI databases to extract dimensions and items for a potential patient-reported outcome scale. The Delphi method was used to modify, add, subtract, and adjust the language of items until the experts reached a consensus on the first draft. This draft was further refined using a cognitive test and a presurvey. The optimized scale was used for a formal survey, and the items were further analyzed and screened using metrics such as the coefficient of variation, correlation coefficient, internal item consistency, factor analysis, reliability, and validity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 10,954 articles were analyzed, and 237 were used to create a pool of 277 patient-reported outcome items. Through two rounds of Delphi expert consultation, the experts' authority coefficients were 0.739 and 0.826. After a cognitive test, several items were adjusted to enhance understanding. Further adjustments were made following a presurvey of 200 advanced breast cancer patients, resulting in a 38-item patient-reported outcomes scale, termed NCC-BC-A. In the national formal survey, 588 advanced breast cancer patients participated. Principal component analysis showed good consistency among the items and sufficient difference between the dimensions. The results were normally distributed with good variation. The Cronbach's <i>α</i> coefficient of the scale was 0.925 and the test–retest reliability was 0.9041.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The NCC-BC-A scale has high validity and reliability. It comprehensively considered the characteristics of systemic treatment for breast cancer, and the specific context within China. Its implementation may help clinicians to pay more attention to quality of life of breast cancer patients and to optimize the system for managing this condition.</p>\u0000 </section>\u0000 </div>","PeriodicalId":100212,"journal":{"name":"Cancer Innovation","volume":"3 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cai2.141","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142449066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
TRIP13: A promising cancer immunotherapy target TRIP13:前景广阔的癌症免疫疗法靶点
Pub Date : 2024-10-11 DOI: 10.1002/cai2.147
Shengnan Jing, Liya Zhao, Liwen Zhao, Yong-Jing Gao, Tianzhen He

The tumor microenvironment (TME) facilitates tumor development through intricate intercellular signaling, thereby supporting tumor growth and suppressing the immune response. Thyroid hormone receptor interactor 13 (TRIP13), an AAA+ ATPase, modulates the conformation of client macromolecules, consequently influencing cellular signaling pathways. TRIP13 has been implicated in processes such as proliferation, invasion, migration, and metastasis during tumor progression. Recent studies have revealed that TRIP13 also plays a role in immune response suppression within the TME. Thus, inhibiting these functions of TRIP13 could potentially enhance immune responses and improve the efficacy of immune checkpoint inhibition. This review summarizes the recent research progress of TRIP13 and discusses the potential of targeting TRIP13 to improve immune-based therapies for patients with cancer.

肿瘤微环境(TME)通过错综复杂的细胞间信号传递促进肿瘤发生,从而支持肿瘤生长并抑制免疫反应。甲状腺激素受体互作因子 13(TRIP13)是一种 AAA+ ATP 酶,可调节客户大分子的构象,从而影响细胞信号通路。TRIP13 与肿瘤进展过程中的增殖、侵袭、迁移和转移等过程有关。最近的研究发现,TRIP13 还在 TME 内的免疫反应抑制中发挥作用。因此,抑制TRIP13的这些功能有可能增强免疫反应,提高免疫检查点抑制剂的疗效。本综述总结了 TRIP13 的最新研究进展,并探讨了靶向 TRIP13 改善癌症患者免疫疗法的潜力。
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引用次数: 0
Impact of metallic nanoparticles on gut microbiota modulation in colorectal cancer: A review 金属纳米粒子对大肠癌肠道微生物群调节的影响:综述
Pub Date : 2024-10-11 DOI: 10.1002/cai2.150
Akash Kumar, Jhilam Pramanik, Kajol Batta, Pooja Bamal, Mukesh Gaur, Sarvesh Rustagi, Bhupendra G. Prajapati, Sankha Bhattacharya

Colorectal cancer (CRC) is the third most prevalent cancer. Ongoing research aims to uncover the causes of CRC, with a growing focus on the role of gut microbiota (GM) in carcinogenesis. The GM influences CRC development, progression, treatment efficacy, and therapeutic toxicities. For example, Fusobacterium nucleatum and Escherichia coli can regulate microbial gene expression through the incorporation of human small noncode RNA and potentially contribute to cancer progression. Metallic nanoparticles (MNPs) have both negative and positive impacts on GM, depending on their type. Several studies state that titanium dioxide may increase the diversity, richness, and abundance of probiotics bacteria, whereas other studies demonstrate dose-dependent GM dysbiosis. The MNPs offer cytotoxicity through the modulation of MAPK signaling pathways, NF-kB signaling pathways, PI3K/Akt signaling pathways, extrinsic signaling pathways, intrinsic apoptosis, and cell cycle arrest at G1, G2, or M phase. MNPs enhance drug delivery, enable targeted therapy, and may restore GM. However, there is a need to conduct well-designed clinical trials to assess the toxicity, safety, and effectiveness of MNPs-based CRC therapies.

大肠癌(CRC)是发病率第三高的癌症。正在进行的研究旨在揭示 CRC 的病因,并越来越多地关注肠道微生物群(GM)在致癌过程中的作用。肠道微生物群会影响 CRC 的发生、发展、治疗效果和治疗毒性。例如,核酸镰刀菌和大肠杆菌可通过结合人类小非编码 RNA 来调节微生物基因表达,并可能导致癌症进展。金属纳米粒子(MNPs)对转基因既有负面影响,也有正面影响,具体取决于其类型。一些研究表明,二氧化钛可增加益生菌的多样性、丰富度和丰度,而其他研究则表明,转基因菌群失调具有剂量依赖性。MNPs 通过调节 MAPK 信号通路、NF-kB 信号通路、PI3K/Akt 信号通路、外在信号通路、内在细胞凋亡以及细胞周期停滞在 G1、G2 或 M 期等途径产生细胞毒性。MNPs 可增强药物输送,实现靶向治疗,并可恢复基因改造。不过,还需要进行设计良好的临床试验,以评估基于 MNPs 的 CRC 疗法的毒性、安全性和有效性。
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引用次数: 0
Breast cancer immunotherapy: Realities and advances 乳腺癌免疫疗法:现实与进步
Pub Date : 2024-09-22 DOI: 10.1002/cai2.140
Aixa Medina, Jeismar Carballo, Eglys González-Marcano, Isaac Blanca, Ana F. Convit

Breast cancer (BC) is the most common malignant tumor and the main cause of death in women worldwide. With increased knowledge regarding tumor escape mechanisms and advances in immunology, many new antitumor strategies such as nonspecific immunotherapies, monoclonal antibodies, anticancer vaccines, and oncolytic viruses, among others, make immunotherapy a promising approach for the treatment of BC. However, these approaches still require meticulous assessment and readjustment as resistance and modest response rates remain important barriers. In this article, we aim to summarize the most recent data available in BC immunotherapy to include the results of ongoing clinical trials and approved therapies used as monotherapies or in combination with conventional treatments.

乳腺癌(BC)是最常见的恶性肿瘤,也是全球女性的主要死因。随着对肿瘤逃逸机制认识的加深和免疫学的进步,许多新的抗肿瘤策略,如非特异性免疫疗法、单克隆抗体、抗癌疫苗和溶瘤病毒等,使免疫疗法成为治疗乳腺癌的一种前景广阔的方法。然而,这些方法仍然需要细致的评估和重新调整,因为耐药性和反应率不高仍然是重要的障碍。在本文中,我们将总结BC免疫疗法的最新数据,包括正在进行的临床试验结果和已获批准的作为单一疗法或与传统疗法联合使用的疗法。
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引用次数: 0
Inetetamab combined with sirolimus and chemotherapy for the treatment of HER2-positive metastatic breast cancer patients with abnormal activation of the PI3K/Akt/mTOR pathway after trastuzumab treatment 伊奈他单抗联合西罗莫司和化疗治疗曲妥珠单抗治疗后PI3K/Akt/mTOR通路异常激活的HER2阳性转移性乳腺癌患者
Pub Date : 2024-09-19 DOI: 10.1002/cai2.145
Qiao Li, Dan Lv, Xiaoying Sun, Mengyuan Wang, Li Cai, Feng Liu, Chenghui Li, Jiuda Zhao, Jing Sun, Yehui Shi, Fei Ma

Background

We explored the efficacy and safety of inetetamab combined with sirolimus and chemotherapy for the treatment of human epidermal factor receptor 2 (HER2)-positive metastatic breast cancer patients with abnormal activation of the PI3K/Akt/mTOR (PAM) pathway after trastuzumab treatment.

Methods

For this prospective multicenter clinical study, HER2-positive metastatic breast cancer patients with PAM pathway mutations confirmed by histology or peripheral blood genetic testing were enrolled from July 2021 to September 2022. Patients were randomly assigned to a trial or control group. The patients in the trial group received inetetamab combined with sirolimus and chemotherapy, while the control group patients received pyrotinib and chemotherapy. The RECIST v1.1 standard was used to evaluate efficacy. Descriptive statistics were used to summarize the clinicopathological features, and the Kaplan–Meier method was used to generate survival curves. The log-rank test was used to compare progression-free survival (PFS) between the two groups.

Results

A total of 59 HER2-positive metastatic breast cancer patients with abnormal activation of the PAM pathway were included, of which 37 received inetetamab combined with sirolimus and chemotherapy treatment and 22 received pyrotinib and chemotherapy treatment. The median PFS was 4.64 months in the inetetamab group and 5.69 months in the pyrotinib group, with no statistically significant difference (p = 0.507). The objective response rates were 27.3% for the inetetamab group and 29.4% for the pyrotinib group. The safety assessment indicated that the adverse event (AE) incidences were 86.1% (31/36) in the inetetamab group and 78.9 (15/19) in the pyrotinib group, with 9 (25%) and four (21.1%) Grade 3/4 AEs in the inetetamab and pyrotinib groups, respectively.

Conclusions

For metastatic HER2-positive breast cancer patients with abnormal PAM pathway activation and previous trastuzumab treatment, the combination of inetetamab with sirolimus and chemotherapy is equivalent to the combination of pyrotinib and chemotherapy. Therefore, this regimen could be a treatment option for PAM pathway-activated metastatic HER2-positive breast cancer patients.

背景 我们探讨了伊奈他单抗联合西罗莫司和化疗治疗曲妥珠单抗治疗后PI3K/Akt/mTOR(PAM)通路异常激活的人表皮因子受体2(HER2)阳性转移性乳腺癌患者的有效性和安全性。 方法 在这项前瞻性多中心临床研究中,2021 年 7 月至 2022 年 9 月期间,招募了经组织学或外周血基因检测证实存在 PAM 通路突变的 HER2 阳性转移性乳腺癌患者。患者被随机分配到试验组和对照组。试验组患者接受伊奈他单抗联合西罗莫司和化疗,对照组患者接受吡罗替尼和化疗。疗效评估采用 RECIST v1.1 标准。描述性统计用于总结临床病理特征,Kaplan-Meier法用于生成生存曲线。采用对数秩检验比较两组患者的无进展生存期(PFS)。 结果 共纳入59例PAM通路异常激活的HER2阳性转移性乳腺癌患者,其中37例接受依替他单抗联合西罗莫司和化疗治疗,22例接受吡罗替尼和化疗治疗。依奈他单抗组的中位生存期为4.64个月,派罗替尼组的中位生存期为5.69个月,差异无统计学意义(P = 0.507)。依奈他单抗组和派罗替尼组的客观反应率分别为27.3%和29.4%。安全性评估显示,依奈他单抗组的不良事件(AE)发生率为86.1%(31/36),派罗替尼组的不良事件发生率为78.9%(15/19),其中依奈他单抗组和派罗替尼组分别发生了9起(25%)和4起(21.1%)3/4级不良事件。 结论 对于PAM通路激活异常且既往接受过曲妥珠单抗治疗的转移性HER2阳性乳腺癌患者,依奈他单抗联合西罗莫司与化疗的疗效等同于吡罗替尼与化疗的疗效。因此,该方案可作为PAM通路激活的转移性HER2阳性乳腺癌患者的治疗选择。
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Cancer Innovation
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