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Antibody-drug conjugates in advanced lung cancer: Is this a new frontier? 晚期肺癌中的抗体-药物共轭物:这是一个新领域吗?
IF 1 Q4 ONCOLOGY Pub Date : 2024-06-01
Joshua E Reuss, Samuel Rosner, Benjamin P Levy

Over the past decade, the lung cancer landscape has been dominated by targeted and immunotherapeutic approaches that have drastically shifted treatment paradigms for patients with advanced non-small cell lung cancer (NSCLC). Despite these scientific and clinical advances, there are still many unmet needs underscoring the importance of novel strategies. Antibody-drug conjugates (ADCs) represent one such strategy that is beginning to alter the therapeutic strategies for patients with advanced NSCLC. The rationale of ADCs is simple: selectively deliver cytotoxic payloads through an antibody-mediated process to target antigens expressed by cancer cells, sparing normal tissue and inflicting damage to tumors. Although this concept has been the leading view, preclinical and clinical observations are demonstrating that only a nascent mechanistic understanding of these agents exists. In this review, we discuss the underlying biology of ADCs and their structure and potential mechanisms of action, examine approved and promising ADC targets in lung cancer, and review emerging ADC targets and combinatorial strategies. Importantly, we address the unanswered questions surrounding ADCs in lung cancer, including biomarker selection, treatment sequencing, and mechanisms of resistance, as well as management of unique ADC-associated toxicities.

在过去的十年中,肺癌的靶向治疗和免疫治疗方法占据了主导地位,这些方法极大地改变了晚期非小细胞肺癌(NSCLC)患者的治疗模式。尽管取得了这些科学和临床进步,但仍有许多需求未得到满足,这凸显了新策略的重要性。抗体药物共轭物(ADC)就是这样一种策略,它开始改变晚期 NSCLC 患者的治疗策略。ADCs 的原理很简单:通过抗体介导的过程选择性地传递细胞毒性有效载荷,靶向癌细胞表达的抗原,保护正常组织并对肿瘤造成损伤。虽然这一概念一直是主流观点,但临床前和临床观察表明,人们对这些制剂的机理认识还处于萌芽阶段。在这篇综述中,我们讨论了 ADC 的基本生物学特性及其结构和潜在作用机制,研究了肺癌中已获批准且前景看好的 ADC 靶点,并回顾了新出现的 ADC 靶点和组合策略。重要的是,我们探讨了与肺癌 ADC 有关的未决问题,包括生物标记物选择、治疗排序、耐药机制以及 ADC 相关毒性的处理。
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引用次数: 0
STEAP1 as a potential target for new therapies in prostate cancer. STEAP1 作为前列腺癌新疗法的潜在靶点。
IF 1 Q4 ONCOLOGY Pub Date : 2024-06-01
Wm Kevin Kelly
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引用次数: 0
Improving survival in metastatic colorectal cancer through optimized patient selection. 通过优化患者选择提高转移性结直肠癌患者的生存率。
IF 1 Q4 ONCOLOGY Pub Date : 2024-06-01
Tanios S Bekaii-Saab, Afsaneh Barzi, Mike Cusnir

The systemic treatment options for patients with metastatic colorectal cancer have recently expanded with the US Food and Drug Administration approval of fruquintinib being added to previously approved trifluridine/tipiracil with or without bevacizumab and regorafenib. These therapies are recommended for use based on the initial clinical trials that focused on their safety and efficacy in extending overall survival of patients with refractory metastatic disease, as well as later studies, including the ReDOS study that confirmed the dose-escalation strategy of regorafenib to be key in optimizing duration of therapy and preventing side effects. Although more research is needed on how to sequence third-line therapies, data from real-world studies showed that switching from regorafenib to trifluridine/tipiracil with or without bevacizumab allowed patients to have a chemotherapy-free break and led to improved survival, suggesting that there may be a benefit for using regorafenib first. Current treatment guidelines state that each therapy can be given before or after the others. Generally, sequencing considerations in the refractory setting include multiple variables such as tumor characteristics, toxicities, factors that are important to the patient, response to prior lines of therapy, and extent of disease.

最近,美国食品和药物管理局批准在以前批准的曲氟啶/替吡拉西与或不与贝伐珠单抗和瑞戈非尼的基础上,增加使用 fruquintinib,从而扩大了转移性结直肠癌患者的全身治疗选择。推荐使用这些疗法的依据是最初的临床试验,这些试验的重点是它们在延长难治性转移性疾病患者总生存期方面的安全性和有效性,以及后来的研究,包括 ReDOS 研究,该研究证实瑞戈非尼的剂量递增策略是优化疗程和预防副作用的关键。虽然如何安排三线疗法的顺序还需要更多的研究,但真实世界的研究数据显示,从瑞戈非尼换成曲氟尿苷/替吡拉西与或不与贝伐珠单抗,可以让患者有一个无化疗的间歇期,并能提高生存率,这表明首先使用瑞戈非尼可能有好处。目前的治疗指南规定,每种疗法可以在其他疗法之前或之后进行。一般来说,难治性治疗的排序考虑因素包括多种变量,如肿瘤特征、毒性、对患者重要的因素、对前几种疗法的反应以及疾病的程度。
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引用次数: 0
Redefining the standard of care for low-grade serous ovarian cancer. 重新定义低级别浆液性卵巢癌的治疗标准。
IF 1 Q4 ONCOLOGY Pub Date : 2024-06-01
Beryl L Manning-Geist, Tal Cantor, Róisín E O'Cearbhaill, Rachel N Grisham

Low-grade serous carcinoma is a rare epithelial ovarian cancer subtype with distinct clinical, histologic, and molecular features. Improved understanding of this disease subtype has prompted recent advances in treatment options. Although low-grade serous carcinoma historically has been treated following a high-grade serous carcinoma paradigm, new data have called into question the utility of platinum retreatment, addressed the possibility of first-line hormonal treatment, and brought forth therapeutic options targeting the MAPK pathway and cyclin D kinase in low-grade tumors. Ongoing research efforts seek to leverage the unique features of low-grade serous carcinoma to refine treatment options for patients with this rare tumor subtype.

低级别浆液性癌是一种罕见的上皮性卵巢癌亚型,具有独特的临床、组织学和分子特征。对这一疾病亚型的进一步了解促使治疗方案取得了最新进展。虽然低级别浆液性癌历来按照高级别浆液性癌的模式进行治疗,但新的数据对铂类再治疗的效用提出了质疑,探讨了一线激素治疗的可能性,并提出了针对低级别肿瘤中 MAPK 通路和细胞周期蛋白 D 激酶的治疗方案。正在进行的研究工作旨在利用低分化浆液性癌的独特特征,完善这一罕见肿瘤亚型患者的治疗方案。
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引用次数: 0
Review of third-line treatment strategies in refractory metastatic colorectal cancer. 难治性转移性结直肠癌的三线治疗策略回顾。
IF 1 Q4 ONCOLOGY Pub Date : 2024-06-01
Afsaneh Barzi
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引用次数: 0
Immune checkpoint inhibitor therapy in locally advanced MSI GI malignancies. 免疫检查点抑制剂治疗局部晚期MSI消化道恶性肿瘤。
IF 1.1 Q4 ONCOLOGY Pub Date : 2024-05-01
Emily C Harrold, Fergus Keane, Andrea Cercek

Locally advanced gastrointestinal (GI) malignancies have conventionally been treated in a multimodal fashion that combines (neo)adjuvant chemotherapy with or without radiation and definitive surgical resection. Clinical data have demonstrated the reduced responsiveness of GI malignancies with microsatellite instability (MSI) to both adjuvant and neoadjuvant systemic chemotherapy when compared with microsatellite stable (MSS) disease. The elevated tumor mutational burden associated with MSI tumors of all types sensitizes these tumors to the effects of immune checkpoint blockade in the metastatic setting, which led to tumor-agnostic approval of immune checkpoint inhibitors in this context. The recent demonstration of greater sensitivity and high pathologic complete response rates to neoadjuvant immunotherapy in locally advanced GI malignancies may ultimately establish a novel treatment paradigm and herald potential nonoperative management of this distinct subgroup of GI malignancies. This article provides an overview of immune checkpoint inhibitor therapy in locally advanced MSI GI malignancies. It also covers the clinical significance of MSI status across the GI cancer spectrum, the available data demonstrating differential responses of MSI and MSS disease to conventional chemotherapy, and the biological rationale for novel strategies utilizing immunotherapy in the neoadjuvant, adjuvant, and nonoperative settings.

局部晚期胃肠道(GI)恶性肿瘤通常采用多模式治疗,即结合或不结合放疗的(新)辅助化疗和明确的手术切除。临床数据表明,与微卫星稳定(MSS)疾病相比,微卫星不稳定(MSI)的消化道恶性肿瘤对辅助化疗和新辅助全身化疗的反应性降低。与各种类型的 MSI 肿瘤相关的肿瘤突变负荷的升高使这些肿瘤在转移情况下对免疫检查点阻断剂的效果敏感,这导致免疫检查点抑制剂在这种情况下获得肿瘤诊断批准。最近的研究表明,局部晚期消化道恶性肿瘤的新辅助免疫疗法具有更高的敏感性和病理完全反应率,这可能最终会建立一种新的治疗模式,并预示着这一独特的消化道恶性肿瘤亚群可能会采用非手术疗法。本文概述了免疫检查点抑制剂治疗局部晚期MSI消化道恶性肿瘤的情况。文章还介绍了MSI状态在消化道癌症中的临床意义、现有数据显示MSI和MSS疾病对常规化疗的不同反应,以及在新辅助治疗、辅助治疗和非手术治疗中利用免疫疗法的新策略的生物学原理。
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引用次数: 0
Improving outcomes in pediatric NTRK gene fusion-positive solid tumors: importance of genomic testing and targeted therapy with the TRK inhibitor larotrectinib. 改善小儿 NTRK 基因融合阳性实体瘤的治疗效果:基因组检测和 TRK 抑制剂 larotrectinib 靶向治疗的重要性。
IF 1 Q4 ONCOLOGY Pub Date : 2024-05-01
Theodore W Laetsch
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引用次数: 0
Increasing inclusion and equity for Black women in breast cancer clinical trials. 提高黑人妇女在乳腺癌临床试验中的包容性和公平性。
IF 1.1 Q4 ONCOLOGY Pub Date : 2024-05-01
Ammanuel Taye, Ahmed Elkhanany, Erica Stringer-Reasor

Black women diagnosed with breast cancer experience a disproportionately high mortality rate. The disparity in outcomes between Black and White women is multifactorial, with a large portion attributed to lower participation of minorities in clinical trials. The lack of diversity in clinical trials continues to both reflect and contribute to health care inequities, limiting the generalizability of research findings. In addition, women who do not enroll in clinical trials miss out on the standard-of-care or often better patient care provided in these trials. Barriers to enrolling diverse populations encompass system-, provider-, and patient-level barriers. Identifying these barriers and providing actionable solutions are key to bolstering enrollment in clinical trials and ultimately eliminating cancer disparities. This review elucidates the barriers to clinical trial participation in Black women diagnosed with breast cancer and discusses ways to overcome these challenges.

被诊断出患有乳腺癌的黑人妇女的死亡率高得不成比例。黑人妇女和白人妇女在治疗结果上的差距是多因素造成的,其中很大一部分原因是少数族裔参与临床试验的比例较低。临床试验缺乏多样性继续反映并助长了医疗保健的不平等,限制了研究结果的推广性。此外,没有参加临床试验的女性也错过了这些试验提供的标准护理或通常更好的患者护理。让不同人群参与临床试验的障碍包括系统、提供者和患者层面的障碍。识别这些障碍并提供可行的解决方案是提高临床试验入组率并最终消除癌症差异的关键。本综述阐明了确诊患有乳腺癌的黑人女性参与临床试验的障碍,并讨论了克服这些挑战的方法。
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引用次数: 0
PROTAC drugs in cancer care. 癌症治疗中的 PROTAC 药物。
IF 1 Q4 ONCOLOGY Pub Date : 2024-05-01
Peter A Fasching
{"title":"PROTAC drugs in cancer care.","authors":"Peter A Fasching","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":51585,"journal":{"name":"Clinical Advances in Hematology & Oncology","volume":"22 4","pages":"188-190"},"PeriodicalIF":1.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140917325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Liver transplant in patients with metastatic colorectal cancer. 转移性结直肠癌患者的肝移植。
IF 1 Q4 ONCOLOGY Pub Date : 2024-05-01
Bashar A Aqel
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引用次数: 0
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Clinical Advances in Hematology & Oncology
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