Cancer treatment reviews最新文献

PARP inhibitors in gliomas: Mechanisms of action, current trends and future perspectives 神经胶质瘤中的 PARP 抑制剂：作用机制、当前趋势和未来展望。

IF 9.6 1区医学 Q1 ONCOLOGY

Cancer treatment reviews

Pub Date : 2024-11-05 DOI: 10.1016/j.ctrv.2024.102850

Eugenia Cella , Alberto Bosio , Pasquale Persico , Mario Caccese , Marta Padovan , Agnese Losurdo , Marta Maccari , Giulia Cerretti , Tamara Ius , Giuseppe Minniti , Ahmed Idbaih , Nader Sanai , Michael Weller , Matthias Preusser , Matteo Simonelli , Giuseppe Lombardi

Gliomas are the most common primary malignant brain tumours in adults. Despite decades of research into novel therapeutic approaches, the prognosis remains poor. PARP1-2 are critical for DNA repair, cell survival and genomic stability and PARP inhibition (PARPi) may be a promising therapeutic approach for gliomas. Inhibition of PARP activity leads to homologous recombination deficiency (HRD), which, in combination with DNA damage, results in cell death. This review summarises the current knowledge and future perspectives of PARPi in glioma. The available literature was reviewed using PubMed, recent major international oncology congresses were consulted, and ongoing clinical trials were searched using ClinicalTrials.gov.

In translational research, PARPi have demonstrated a strong scientific rationale for their use in the treatment of glioma. They have been evaluated both alone and in combination with radiotherapy, temozolomide, anti-angiogenic agents, immunotherapy and other new drugs in newly diagnosed or recurrent glioma. Most studies were open-label, non-randomised, dose-escalation phase I-II trials. Early results show promising anti-tumour activity, and key challenges include identifying predictive biomarkers, elucidating synergistic effects in combination therapies, addressing the development of resistance, and managing hematological toxicity.

In conclusion, early phase studies have shown promising anti-tumour activity of PARPi that should be confirmed in larger prospective and randomised trials. In addition, the development of novel PARPi with improved blood brain barrier (BBB) penetration and PARP inhibitor activity with new synergistic treatment combinations seems promising and needs to be further explored.

胶质瘤是成人最常见的原发性恶性脑肿瘤。尽管对新型治疗方法进行了数十年的研究，但预后仍然很差。PARP1-2对DNA修复、细胞存活和基因组稳定性至关重要，抑制PARP（PARPi）可能是治疗胶质瘤的一种有前景的方法。抑制PARP活性会导致同源重组缺陷（HRD），而HRD与DNA损伤相结合会导致细胞死亡。本综述总结了PARPi在胶质瘤中的现有知识和未来展望。我们使用 PubMed 查阅了现有文献，参考了近期的主要国际肿瘤学大会，并使用 ClinicalTrials.gov 搜索了正在进行的临床试验。在转化研究中，PARPi 已经证明了其用于治疗胶质瘤的强大科学依据。在新诊断或复发胶质瘤的治疗中，对 PARPi 单独使用或与放疗、替莫唑胺、抗血管生成剂、免疫疗法和其他新药联合使用进行了评估。大多数研究都是开放标签、非随机、剂量递增的 I-II 期试验。早期研究结果显示了良好的抗肿瘤活性，面临的主要挑战包括确定预测性生物标志物、阐明联合疗法的协同效应、解决耐药性的产生以及控制血液毒性。总之，早期研究显示 PARPi 具有良好的抗肿瘤活性，应在更大规模的前瞻性随机试验中加以证实。此外，开发具有更好的血脑屏障（BBB）穿透性和 PARP 抑制剂活性的新型 PARPi 以及新的协同治疗组合似乎很有希望，需要进一步探索。

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引用次数: 0

Optimizing outcomes and personalizing care with targeted agents in advanced cholangiocarcinoma 在晚期胆管癌中使用靶向药物优化疗效和个性化治疗。

IF 9.6 1区医学 Q1 ONCOLOGY

Cancer treatment reviews

Pub Date : 2024-11-05 DOI: 10.1016/j.ctrv.2024.102851

Umair Mahmood , Ahmed Abbass , Khurum Khan

Traditional chemotherapy and immunotherapy-based systemic treatments for locally advanced or metastatic cholangiocarcinoma have been associated with poor clinical outcomes driven partly by molecular heterogeneity promoting early treatment resistance and a higher toxicity profile associated with these regimens. Few patients are eligible for upfront surgical resection and clinical studies have been traditionally difficult to conduct due to the orphan nature of this disease. However, increasing use of genomic profiling in clinical practice have led to active investigations of aberrant albeit promising mechanistic therapeutic targets such as IDH-1, FGFRs, BRAF^V600E, HER-2 and NTRK.

This review article aims to highlight the complex genomic landscape of this difficult-to-treat disease, followed by a discussion of evidence-based biological mechanisms that can be actioned using targeted agents. We explore the clinical rationale behind a targeted therapeutic strategy, the role of liquid biopsies in guiding clinical decisions and future treatment pathways for cholangiocarcinoma management. We also discuss the challenges and opportunities originating from recent clinical trials evaluating targeted treatments and our own institutional experience at UCLH that have aimed to address some of these biological complexities and have translated into improved patient outcomes via effective molecularly driven patient selection strategies. We also provide perspectives on emerging novel, next generation targeted inhibitors overcoming treatment resistance to previous targeted agents with demonstrated clinical value in a challenging patient population.

对于局部晚期或转移性胆管癌，传统的化疗和免疫治疗为主的全身治疗方法临床疗效不佳，部分原因是分子异质性导致早期耐药，以及这些治疗方案的毒性较高。符合前期手术切除条件的患者很少，而且由于这种疾病的孤儿性质，临床研究历来难以开展。然而，临床实践中越来越多地使用基因组剖析技术，这促使人们积极研究异常但有希望的机理治疗靶点，如 IDH-1、FGFR、BRAFV600E、HER-2 和 NTRK。这篇综述文章旨在强调这种难治疾病复杂的基因组状况，然后讨论可使用靶向药物的循证生物机制。我们探讨了靶向治疗策略背后的临床原理、液体活检在指导临床决策中的作用以及胆管癌治疗的未来治疗途径。我们还讨论了近期评估靶向治疗的临床试验所带来的挑战和机遇，以及我们自己在 UCLH 的机构经验，这些经验旨在解决其中一些复杂的生物学问题，并通过有效的分子驱动患者选择策略改善患者预后。我们还对新出现的下一代靶向抑制剂进行了展望，这些抑制剂克服了以往靶向药物的耐药性，并在具有挑战性的患者群体中证明了其临床价值。

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引用次数: 0

Local administration of immunotherapy for patients with skin cancer: A systematic review 对皮肤癌患者进行局部免疫治疗：系统回顾

IF 9.6 1区医学 Q1 ONCOLOGY

Cancer treatment reviews

Pub Date : 2024-10-28 DOI: 10.1016/j.ctrv.2024.102848

J.C. Janssen , B. van Dijk , L.L. Hoeijmakers , D.J. Grünhagen , W.M. Bramer , C. Verhoef , T.D. de Gruijl , C.U. Blank , A.A.M. van der Veldt

Since the introduction of immune checkpoint inhibitors (ICIs) targeting PD-1 and CTLA-4 receptors, survival has improved significantly for patients with irresectable and metastatic skin cancer, including cutaneous squamous cell cancer and melanoma. However, systemic administration of these drugs is associated with immune related adverse events (irAEs), which can be severe, irreversible and even fatal. To reduce the risk of irAEs associated with systemic exposure to immunotherapeutic drugs, local administration of low doses could be considered. This systematic review provides an overview of early phase clinical trials with drugs that are currently under investigation for intratumoral administration in patients with melanoma and non-melanoma skin cancer.

自以 PD-1 和 CTLA-4 受体为靶点的免疫检查点抑制剂（ICIs）问世以来，包括皮肤鳞状细胞癌和黑色素瘤在内的不可切除和转移性皮肤癌患者的生存率得到了显著提高。然而，这些药物的全身用药与免疫相关不良事件（irAEs）有关，这些不良事件可能是严重的、不可逆的，甚至是致命的。为了降低全身暴露于免疫治疗药物所带来的irAEs风险，可以考虑小剂量局部用药。本系统综述概述了目前正在研究的用于黑色素瘤和非黑色素瘤皮肤癌患者瘤内给药的早期临床试验。

引用次数: 0

False Positive Rate from Prospective Studies of PET-CT in Cutaneous Malignant Melanoma: A Systematic Review and Meta-Analysis 皮肤恶性黑色素瘤 PET-CT 前瞻性研究的假阳性率：系统性回顾和元分析。

IF 9.6 1区医学 Q1 ONCOLOGY

Cancer treatment reviews

Pub Date : 2024-10-24 DOI: 10.1016/j.ctrv.2024.102849

B. Smith , J. Church-Martin , H. Abed , E. Lloyd , J.T. Hardwicke

Background

Cutaneous malignant melanoma (CMM) is increasing in prevalence and possesses the highest mortality rate of any skin cancer. Positron Emission Tomography and Computed Tomography (PET-CT) may be utilised in either radiological staging or surveillance, primarily in stage III-IV disease. False positive (FP) results lead to patient distress, increased costs, and unnecessary follow-up. The FP rate in CMM literature varies widely, altering calculations of positive predictive value and has not undergone pooled meta-analytic.

Materials and Methods

A systematic review and meta-analysis of FP results in prospective studies of PET-CT in CMM was performed in accordance with PRISMA guidelines.

Results

The systematic review produced 14 trials for inclusion. Patient-based reporting had the lowest pooled proportion of FP results with 5.8 % (95 % CI = 3.3 % to 8.8 %), lesion-based was highest with 9.1 % (95 % CI = 3.4 % to 17.2 %) and combined was 6.1 % (95 % CI = 4.3 % to 8.1 %). Bias was low to unclear other than for FP reporting. Heterogeneity (I2) was variable across all analyses. FP findings were mainly lymphatic, dermatological, respiratory, or skeletal. Diagnostic information was not provided.

Conclusions

This study was the first attempt to quantify the pooled proportion of FP results from PET-CT in CMM. A small number of studies (n = 14) were available due to the predominance of retrospective methodology. Due to inconsistent reporting the true proportion of FP results is unclear. Systemic distribution was expected but limited diagnostic information was provided. Repeat meta-analysis using retrospective work should be performed. Future work should be prospective with clearly documented FP proportion, distribution, diagnosis, and follow-up.

背景：皮肤恶性黑色素瘤（CMM）的发病率越来越高，是死亡率最高的皮肤癌。正电子发射断层扫描和计算机断层扫描（PET-CT）可用于放射学分期或监测，主要用于 III-IV 期疾病。假阳性（FP）结果会导致患者痛苦、费用增加和不必要的随访。CMM文献中的假阳性率差异很大，改变了阳性预测值的计算方法，而且尚未进行集合荟萃分析：根据PRISMA指南，对PET-CT用于CMM的前瞻性研究的FP结果进行了系统回顾和荟萃分析：结果：系统综述共纳入了 14 项试验。基于患者报告的FP结果汇总比例最低，为5.8%（95% CI = 3.3%至8.8%），基于病灶报告的FP结果汇总比例最高，为9.1%（95% CI = 3.4%至17.2%），合并报告的FP结果汇总比例为6.1%（95% CI = 4.3%至8.1%）。除 FP 报告外，其他偏倚较低，甚至不明显。所有分析的异质性（I2）均不相同。FP结果主要涉及淋巴、皮肤、呼吸或骨骼。未提供诊断信息：本研究首次尝试量化CMM PET-CT的FP结果汇总比例。由于主要采用回顾性方法，因此研究数量较少（n = 14）。由于报告不一致，FP结果的真实比例尚不清楚。预计会有系统性分布，但提供的诊断信息有限。应使用回顾性方法进行重复荟萃分析。今后的工作应采用前瞻性方法，明确记录FP的比例、分布、诊断和随访情况。

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引用次数: 0

Corrigendum to “Navigating the complex relationship between human gut microbiota and breast cancer: Physiopathological, prognostic and therapeutic implications” [Cancer Treat. Rev. 130 (2024) 102816] 人类肠道微生物群与乳腺癌之间的复杂关系：Cancer Treat. Rev. 130 (2024) 102816]的更正。

IF 9.6 1区医学 Q1 ONCOLOGY

Cancer treatment reviews

Pub Date : 2024-10-19 DOI: 10.1016/j.ctrv.2024.102844

F. Schettini , F. Gattazzo , S. Nucera , E. Rubio Garcia , R. López-Aladid , L. Morelli , A. Fontana , P. Vigneri , C. Casals-Pascual , V. Iebba , D. Generali

引用次数: 0

Diagnosis and management of dedifferentiated liposarcoma: A multidisciplinary position statement 诊断和处理已分化脂肪肉瘤：多学科立场声明。

IF 9.6 1区医学 Q1 ONCOLOGY

Cancer treatment reviews

Pub Date : 2024-10-18 DOI: 10.1016/j.ctrv.2024.102846

Candace L. Haddox , Jason L. Hornick , Christina L. Roland , Elizabeth H. Baldini , Vicki L. Keedy , Richard F. Riedel

Dedifferentiated liposarcoma (DDLPS) is a malignant mesenchymal neoplasm in desperate need of novel therapeutic approaches. Often occurring in conjunction with well-differentiated liposarcoma (WDLPS), DDLPS can behave more aggressively and exhibits a significant risk for developing recurrence or metastatic disease when compared to its well-differentiated counterpart. A multidisciplinary approach is critically important, particularly for patients with localized disease, as disease presentations are often complex, and the management of patients has become increasingly nuanced as treatment approaches have become more refined. Expert pathology review and appropriate application of diagnostic molecular techniques are key components of DDLPS diagnosis and also reflect an improved understanding of the underlying pathogenesis of the disease. Systemic therapies remain limited for DDLPS, but novel therapies targeting important underlying molecular drivers have resulted in ongoing clinical trials aiming to improve outcomes for patients with advanced disease. In recognition of the increased activity and interest within the DDLPS field, a multidisciplinary group of nationally recognized experts in medical oncology, surgical oncology, radiation oncology, and pathology was convened to summarize key insights. This position paper highlights important points from the meeting and provides evidence-based recommendations for practicing clinicians.

未分化脂肪肉瘤（DDLPS）是一种恶性间质肿瘤，急需新型治疗方法。DDLPS通常与分化良好的脂肪肉瘤（WDLPS）同时发生，与分化良好的脂肪肉瘤相比，DDLPS的侵袭性更强，复发或转移的风险也更大。多学科治疗方法至关重要，尤其是对局部疾病患者而言，因为疾病的表现往往很复杂，而且随着治疗方法的不断完善，对患者的管理也变得越来越微妙。病理专家的审查和分子诊断技术的适当应用是 DDLPS 诊断的关键要素，同时也反映了人们对该疾病潜在发病机制的进一步了解。针对 DDLPS 的系统疗法仍然有限，但针对重要潜在分子驱动因素的新型疗法已导致正在进行的临床试验，旨在改善晚期患者的预后。鉴于 DDLPS 领域的活动和兴趣日益增加，一个由国内知名的肿瘤内科、肿瘤外科、肿瘤放射科和病理科专家组成的多学科小组召开了会议，以总结关键见解。本立场文件重点介绍了会议的重要观点，并为临床医生提供了循证建议。

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引用次数: 0

Safety and efficacy of antibody-drug conjugates plus immunotherapy in solid tumours: A systematic review and meta-analysis 抗体药物结合物加免疫疗法治疗实体瘤的安全性和有效性：系统综述与荟萃分析。

IF 9.6 1区医学 Q1 ONCOLOGY

Cancer treatment reviews

Pub Date : 2024-10-18 DOI: 10.1016/j.ctrv.2024.102847

Guillermo Villacampa , Pablo Cresta Morgado , Lorenzo Carità , Victor Navarro , Tomas Pascual , Rodrigo Dienstmann

Background

Combining antibody-drug conjugate (ADCs) with immune checkpoint inhibitors (ICIs) is emerging as a promising treatment option to increase efficacy outcomes. However, concerns arise regarding the safety of these combinations, as some toxicities may overlap. Currently, there is still limited information about the safety profiles of this strategy.

Methods

A systematic review and meta-analysis was conducted to identify clinical trials investigating FDA-approved ADCs in combination with ICI drugs in the metastatic setting across all solid tumors. The primary endpoint of this study was the percentage of adverse events (AEs) of any grade and grade

\geq

3. Secondary endpoints include the percentage of patients with AEs leading to death, treatment discontinuation, proportion of complete responses (CR) and overall response rate (ORR). A parallel search was conducted to quantify the safety profile of ADCs and ICIs in monotherapy. Random effects models were used to estimate pooled outcomes.

Results

Sixteen trials involving 1,133 patients treated with ADC plus ICI met the inclusion criteria with six different ADCs evaluated. Overall, 55.3 % of patients developed grade ≥ 3 AEs, 30.0 % of patients had treatment discontinuation, and 3.0 % experienced AEs leading to death. When compared to trials evaluating ADC or ICI as monotherapy, the combination results in similar rates of the most common AEs. However, it increases the risk of specific toxicities, such as ILD/pneumonitis (15.0 % with T-DXd plus ICI vs. 11.5 % with T-DXd alone). The pooled ORR was 48.8 % (95 %CI 39.4 % – 58.4 %) and the CR rate was 9.0 % (95 %CI 5.5 – 14.5). PD-L1-positive tumors showed numerically better efficacy outcomes.

Conclusions

This meta-analysis shows that the safety profile of the ADC plus ICI is comparable to that of ADC monotherapy. However, it increases the risk of certain toxicities of special interest, such as ILD/pneumonitis, highlighting the need for careful monitoring.

背景：抗体药物共轭物（ADCs）与免疫检查点抑制剂（ICIs）的结合正在成为一种有希望提高疗效的治疗方案。然而，由于某些毒性可能会重叠，人们对这些组合的安全性产生了担忧。目前，有关这一策略安全性的信息仍然有限：方法：我们进行了一项系统性回顾和荟萃分析，以确定在所有实体瘤的转移性治疗中研究 FDA 批准的 ADC 与 ICI 药物联用的临床试验。本研究的主要终点是任何级别和级别≥3的不良事件（AEs）的百分比。次要终点包括AEs导致死亡、治疗中止、完全应答（CR）比例和总应答率（ORR）的患者比例。为量化 ADC 和 ICIs 单药治疗的安全性，还进行了平行检索。随机效应模型用于估计汇总结果：有16项试验符合纳入标准，涉及1133名接受ADC加ICI治疗的患者，对6种不同的ADC进行了评估。总体而言，55.3%的患者出现了≥3级的AEs，30.0%的患者中断了治疗，3.0%的患者出现了导致死亡的AEs。与评估 ADC 或 ICI 作为单一疗法的试验相比，联合疗法导致的最常见 AEs 发生率相似。然而，联合用药会增加特定毒性反应的风险，如ILD/肺炎（T-DXd加ICI为15.0%，单用T-DXd为11.5%）。总ORR为48.8%（95%CI为39.4% - 58.4%），CR为9.0%（95%CI为5.5 - 14.5）。PD-L1阳性肿瘤的疗效更好：这项荟萃分析表明，ADC 加 ICI 的安全性与 ADC 单药治疗相当。然而，它增加了某些特别值得关注的毒性反应的风险，如ILD/肺炎，这就突出了仔细监测的必要性。

{"title":"Safety and efficacy of antibody-drug conjugates plus immunotherapy in solid tumours: A systematic review and meta-analysis","authors":"Guillermo Villacampa , Pablo Cresta Morgado , Lorenzo Carità , Victor Navarro , Tomas Pascual , Rodrigo Dienstmann","doi":"10.1016/j.ctrv.2024.102847","DOIUrl":"10.1016/j.ctrv.2024.102847","url":null,"abstract":"<div><h3>Background</h3><div>Combining antibody-drug conjugate (ADCs) with immune checkpoint inhibitors (ICIs) is emerging as a promising treatment option to increase efficacy outcomes. However, concerns arise regarding the safety of these combinations, as some toxicities may overlap. Currently, there is still limited information about the safety profiles of this strategy.</div></div><div><h3>Methods</h3><div>A systematic review and meta-analysis was conducted to identify clinical trials investigating FDA-approved ADCs in combination with ICI drugs in the metastatic setting across all solid tumors. The primary endpoint of this study was the percentage of adverse events (AEs) of any grade and grade <span><math><mo>≥</mo></math></span> 3. Secondary endpoints include the percentage of patients with AEs leading to death, treatment discontinuation, proportion of complete responses (CR) and overall response rate (ORR). A parallel search was conducted to quantify the safety profile of ADCs and ICIs in monotherapy. Random effects models were used to estimate pooled outcomes.</div></div><div><h3>Results</h3><div>Sixteen trials involving 1,133 patients treated with ADC plus ICI met the inclusion criteria with six different ADCs evaluated. Overall, 55.3 % of patients developed grade ≥ 3 AEs, 30.0 % of patients had treatment discontinuation, and 3.0 % experienced AEs leading to death. When compared to trials evaluating ADC or ICI as monotherapy, the combination results in similar rates of the most common AEs. However, it increases the risk of specific toxicities, such as ILD/pneumonitis (15.0 % with T-DXd plus ICI vs. 11.5 % with T-DXd alone). The pooled ORR was 48.8 % (95 %CI 39.4 % – 58.4 %) and the CR rate was 9.0 % (95 %CI 5.5 – 14.5). PD-L1-positive tumors showed numerically better efficacy outcomes.</div></div><div><h3>Conclusions</h3><div>This meta-analysis shows that the safety profile of the ADC plus ICI is comparable to that of ADC monotherapy. However, it increases the risk of certain toxicities of special interest, such as ILD/pneumonitis, highlighting the need for careful monitoring.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"131 ","pages":"Article 102847"},"PeriodicalIF":9.6,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Neoadjuvant immunotherapy strategies for resectable non-small cell lung cancer (NSCLC): Current evidence among special populations and future perspectives 针对可切除非小细胞肺癌（NSCLC）的新辅助免疫疗法策略：特殊人群的现有证据与未来展望。

IF 9.6 1区医学 Q1 ONCOLOGY

Cancer treatment reviews

Pub Date : 2024-10-16 DOI: 10.1016/j.ctrv.2024.102845

Claudia Parisi , Pamela Abdayem , Marco Tagliamento , Benjamin Besse , David Planchard , Jordi Remon , Gabriele Minuti , Federico Cappuzzo , Fabrice Barlesi

About one third of patients with Non-Small Cell Lung Cancer (NSCLC) presents at diagnosis with localized or locally advanced disease amenable to curative surgical resection. Surgical operability refers to stage I to IIIA and selected stage IIIB NSCLC. One of the main challenges in the management of early-stage resectable NSCLC is the optimization of available therapeutic strategies to prevent local and distant disease relapse, thus improving survival outcomes. There is evidence supporting the clinical use of both adjuvant and neoadjuvant immunotherapy-based strategies for resected/resectable, stage IB-IIIA NSCLC. Available data from randomized phase III trials have led to the incorporation of several immune checkpoint blockers (ICBs) into the international guidelines for early-stage NSCLC. Preclinical rationale of targeting specific subsets of T-cells by acting early on immune checkpoint receptors (e.g., PD-(L)1 and CTLA-4) is strong. Recent evidence is in favor of the neoadjuvant approach alone or as a part of perioperative strategy, demonstrating survival benefit. Combining neoadjuvant chemotherapy and immunotherapy before surgery results in both pathologic complete response (pCR) and major pathologic response (MPR) improvement, and survival outcomes, with no major safety issues. In this review, we summarize the rationale behind neoadjuvant/perioperative immunotherapy strategies and, due to the clinical relevance of immunotherapy in resectable NSCLC, we provide current evidence of this cutting-edge approach among special populations including older adults, women, and oncogene addicted NSCLC. To conclude, we present future perspectives in the use of immunotherapy for operable NSCLC with a special focus on novel investigational combinations underway.

约有三分之一的非小细胞肺癌（NSCLC）患者在确诊时为局部或局部晚期疾病，可进行根治性手术切除。可手术指的是 I 至 IIIA 期和部分 IIIB 期 NSCLC。治疗早期可切除 NSCLC 的主要挑战之一是优化现有治疗策略，防止局部和远处疾病复发，从而改善生存预后。有证据支持将基于辅助和新辅助免疫疗法的策略用于临床治疗已切除/可切除的 IB-IIIA 期 NSCLC。随机III期试验的现有数据促使一些免疫检查点阻断剂（ICB）被纳入早期NSCLC的国际指南。通过早期作用于免疫检查点受体（如PD-(L)1和CTLA-4）来靶向特定T细胞亚群的临床前理论依据非常充分。最近有证据表明，新辅助治疗方法单独使用或作为围手术期策略的一部分使用均可使患者生存获益。在手术前联合使用新辅助化疗和免疫疗法可改善病理完全反应（pCR）和主要病理反应（MPR），提高生存率，且无重大安全性问题。在这篇综述中，我们总结了新辅助/围手术期免疫疗法策略背后的原理，由于免疫疗法在可切除NSCLC中的临床意义，我们提供了这一前沿方法在特殊人群（包括老年人、女性和癌基因成瘾的NSCLC）中的现有证据。最后，我们介绍了免疫疗法用于可手术 NSCLC 的未来前景，并特别关注了正在进行的新型研究组合。

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引用次数: 0

Crosstalk and communication of cancer-associated fibroblasts with natural killer and dendritic cells: New frontiers and unveiled opportunities for cancer immunotherapy 癌症相关成纤维细胞与自然杀伤细胞和树突状细胞之间的相互作用和交流：癌症免疫疗法的新领域和新机遇。

IF 9.6 1区医学 Q1 ONCOLOGY

Cancer treatment reviews

Pub Date : 2024-10-15 DOI: 10.1016/j.ctrv.2024.102843

Simone Ielpo , Francesca Barberini , Farnaz Dabbagh Moghaddam , Silvia Pesce , Chiara Cencioni , Francesco Spallotta , Adele De Ninno , Luca Businaro , Emanuela Marcenaro , Roberto Bei , Loredana Cifaldi , Giovanni Barillari , Ombretta Melaiu

Natural killer (NK) cells and dendritic cells (DCs) are critical mediators of anti-cancer immune responses. In addition to their individual roles, NK cells and DCs are involved in intercellular crosstalk which is essential for the initiation and coordination of adaptive immunity against cancer. However, NK cell and DC activity is often compromised in the tumor microenvironment (TME). Recently, much attention has been paid to one of the major components of the TME, the cancer-associated fibroblasts (CAFs), which not only contribute to extracellular matrix (ECM) deposition and tumor progression but also suppress immune cell functions. It is now well established that CAFs support T cell exclusion from tumor nests and regulate their cytotoxic activity. In contrast, little is currently known about their interaction with NK cells, and DCs. In this review, we describe the interaction of CAFs with NK cells and DCs, by secreting and expressing various mediators in the TME of adult solid tumors. We also provide a detailed overview of ongoing clinical studies evaluating the targeting of stromal factors alone or in combination with immunotherapy based on immune checkpoint inhibitors. Finally, we discuss currently available strategies for the selective depletion of detrimental CAFs and for a better understanding of their interaction with NK cells and DCs.

自然杀伤细胞（NK）和树突状细胞（DC）是抗癌免疫反应的关键介质。除了各自的作用外，NK细胞和树突状细胞还参与细胞间串联，这对于启动和协调抗癌适应性免疫至关重要。然而，在肿瘤微环境（TME）中，NK 细胞和 DC 的活性往往会受到损害。癌症相关成纤维细胞（CAFs）不仅有助于细胞外基质（ECM）沉积和肿瘤进展，还能抑制免疫细胞的功能。目前已经证实，CAFs 支持 T 细胞从肿瘤巢穴中排除，并调节其细胞毒性活性。相比之下，目前人们对 CAFs 与 NK 细胞和 DC 的相互作用知之甚少。在这篇综述中，我们描述了 CAFs 通过分泌和表达成人实体瘤 TME 中的各种介质与 NK 细胞和 DCs 的相互作用。我们还详细综述了正在进行的临床研究，这些研究评估了单独或与基于免疫检查点抑制剂的免疫疗法相结合的基质因子靶向治疗。最后，我们讨论了目前可用的选择性清除有害 CAFs 的策略，以及更好地了解它们与 NK 细胞和 DCs 相互作用的策略。

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引用次数: 0

Advances and challenges in immunotherapy for locally advanced nasopharyngeal carcinoma 局部晚期鼻咽癌免疫疗法的进展与挑战。

IF 9.6 1区医学 Q1 ONCOLOGY

Cancer treatment reviews

Pub Date : 2024-10-11 DOI: 10.1016/j.ctrv.2024.102840

Miaoying Cai , Yifu Wang , Huangrong Ma , Li Yang , Zhiyuan Xu

Nasopharyngeal carcinoma (NPC) is a prevalent malignant tumor of the head and neck, with approximately 70 % of patients being diagnosed at a locally advanced stage. Despite the responsiveness to radiotherapy and chemotherapy, the 5-year survival rate of locally advanced NPC (LANPC) remains at approximately 80 %. Hence, there is an urgent need for novel treatment strategies to improve the prognosis of patients with LANPC. Numerous studies have illustrated the efficacy of immune checkpoint inhibitors (ICIs) in recurrent/metastatic NPC. Hence, the potential of immunotherapy for LANPC is under investigation. Using the Web of Clinical Trials, we identified 84 relevant trials exploring immunotherapy for NPC, encompassing 17 trials focusing on ICIs for LANPC. Preliminary findings from several trials suggest that adding ICIs into the primary treatment for LANPC significantly enhances the objective response rate and progression-free survival, with manageable safety profiles. However, the type, dosage, and timing of integration (induction phase, concurrent phase, and adjuvant phase) of ICIs into standard primary treatment of LANPC varies among these trials and further researches are warranted. This review provides an overview of immunotherapy principles in NPC, discusses recent advances and challenges associated with ICIs in the primary treatment for LANPC derived from published and ongoing clinical trials, and outlines the current landscape of other immunotherapies in LANPC, such as adoptive cell therapy, immunomodulatory agents, and tumor vaccines in LANPC. These insights aim to inform clinical practice and guide future researches.

鼻咽癌（NPC）是一种常见的头颈部恶性肿瘤，约 70% 的患者被诊断为局部晚期。尽管对放疗和化疗有反应，但局部晚期鼻咽癌（LANPC）的 5 年生存率仍约为 80%。因此，迫切需要新的治疗策略来改善局部晚期鼻咽癌患者的预后。大量研究表明，免疫检查点抑制剂（ICIs）对复发/转移性鼻咽癌具有疗效。因此，免疫疗法治疗 LANPC 的潜力正在研究之中。通过临床试验网，我们确定了 84 项探索鼻咽癌免疫疗法的相关试验，其中包括 17 项针对 LANPC 的 ICIs 试验。几项试验的初步结果表明，将 ICIs 加入 LANPC 的主要治疗中可显著提高客观反应率和无进展生存期，且安全性可控。然而，在这些试验中，将 ICIs 纳入 LANPC 标准初治的类型、剂量和时间（诱导期、同期期和辅助期）各不相同，因此有必要开展进一步研究。本综述概述了鼻咽癌的免疫疗法原理，讨论了已发表和正在进行的临床试验中与 ICIs 在 LANPC 初级治疗中相关的最新进展和挑战，并概述了 LANPC 中其他免疫疗法的现状，如 LANPC 中的收养细胞疗法、免疫调节药物和肿瘤疫苗。这些见解旨在为临床实践提供信息并指导未来的研究。

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引用次数: 0