食管癌新辅助治疗研究新进展

食管癌作为全球常见肿瘤之一,其发病率及死亡率较高,发现时多为中晚期,实现有效治疗目标仍具挑战性。当前新辅助治疗策略,包括化疗、放疗、分子靶向、免疫治疗及综合治疗,在临床中的价值得到广泛认可,但不同方案的选择存在一定争议。本文结合相关文献对食管癌新辅助治疗方法的研究现状及进展进行了总结和概述,并对其应用前景和存在的问题进行了分析,为进一步优化临床诊疗策略提供参考。

恶性淋巴瘤的精准治疗进展

恶性淋巴瘤在血液肿瘤中的发病率位列第一,是世界发病率较高的十大肿瘤之一,近年来发病率仍在持续升高,其亚型众多,且具有较高的异质性[1]。按照其病理类型,可分为霍奇金淋巴瘤(Hodgkin lymphoma,HL)和非霍奇金淋巴瘤(non-Hodgkin lymphoma,NHL)。既往治疗淋巴瘤的手段包括外科手术、放疗、化疗,但复发/难治一直是较为棘手的难题。近年来靶向治疗、免疫治疗、细胞治疗等的发展,给淋巴瘤患者带来新的曙光。相较于传统治疗直接杀灭肿瘤细胞,这些治疗方法则通过特定通路增强免疫细胞的抗肿瘤效应发挥作用。这些药物干预也推动了精准靶向治疗和个体化治疗的发展。现分析近年来多种精准治疗方法在恶性淋巴瘤中的研究成果。

3例恶性腹膜间皮瘤的临床表现和基因突变特点分析及文献回顾

目的:分析恶性腹膜间皮瘤(malignant peritoneal mesothelioma,MPeM)患者的临床表现和基因突变特点,观察疾病治疗效果,寻找潜在的靶向和免疫治疗方案。方法:收集2019年12月至2020年9月在我院妇产科收治的3例MPeM患者,对其临床表现、治疗过程及基因突变特点进行分析,并随访其治疗效果及预后。结果:3例MPeM患者,发病年龄为66~70岁,均无石棉暴露史,PCI评分为36~39分,根据病情选择了不同术式,术后进行腹腔灌注或静脉化疗。基因检测结果发现了BAP1、CSF1R、CDKN2A、NF2四个可能具有临床意义的突变,其中CSF1R突变首次在MPeM患者中被发现。3例患者的总生存期为2.2~9.6个月。结论:高龄且肿瘤负荷重的MPeM患者预后较差,应推荐所有明确诊断的MPeM患者进行基因检测,以寻求可能的靶向/免疫治疗获益。

局部进展期直肠癌新辅助治疗研究进展

目的分析各新辅助治疗策略的优劣,为临床诊疗提供参考,并为进一步研究探索提供方向。方法检索并查阅近年来国内外医学数据库(PubMed、EMBASE、Cochrane Library、维普数据库、中国知网、万方数据库等),对局部进展期直肠癌新辅助治疗的相关文献进行综述。结果新辅助治疗可以降低肿瘤分期、提高保肛率、降低局部复发率,但并未显著降低远处转移率和侧方淋巴结转移率,也未改善长期生存。越来越多的优化新辅助方案应运而生。分子靶向药物和免疫治疗正被尝试应用于临床,结合新兴生物学标志物的研究,以提高局部进展期直肠癌患者的疗效,并减少治疗相关副作用,改善患者的生存获益。结论新辅助治疗是局部进展期直肠癌标准治疗策略,对新辅助治疗模式的探索有望进一步提高治疗效果、减轻毒副反应,并改善生存预后。通过结合肿瘤分子生物学指标识别和筛选获益人群,有望成为未来研究的重要方向。

Cellular immunity augmentation in mainstream oncologic therapy

Anticancer immunotherapy has undergone a long evolving journey for decades, and has been dramatically applied to mainstream treatments in oncology in recent 5 years. This progress represents an advanced milestone following cytotoxic medicine and targeted therapy. Cellular immunity plays a pivotal role in the immune responses of hosts to tumor antigens. Such immunity is notably suppressed during neoplastic progression due to immuno-editing processes. Cellular immunity can also be selectively reactivated to combat malignancies while exploiting the advantages of contemporary scientific breakthroughs in molecular immunology and genetic engineering. The rapid advancement of cellular immunity-based therapeutic approaches has achieved high efficacy in certain cancer patients. Consequently, the landscape of oncologic medicine and pharmaceutical innovation has transformed recently. In this regard, we present a comprehensive update on clinically established anti-cancer treatments with cell immunity augmentation as the major mechanism of action.

Combining targeted therapy and immune checkpoint inhibitors in the treatment of metastatic melanoma

Melanoma is the deadliest form of skin cancer and has an incidence that is rising faster than any other solid tumor. Metastatic melanoma treatment has considerably progressed in the past five years with the introduction of targeted therapy(BRAF and MEK inhibitors) and immune checkpoint blockade(anti-CTLA4, anti-PD-1, and anti-PD-L1). However, each treatment modality has limitations. Treatment with targeted therapy has been associated with a high response rate, but with short-term responses. Conversely, treatment with immune checkpoint blockade has a lower response rate, but with longterm responses. Targeted therapy affects antitumor immunity, and synergy may exist when targeted therapy is combined with immunotherapy. This article presents a brief review of the rationale and evidence for the potential synergy between targeted therapy and immune checkpoint blockade. Challenges and directions for future studies are also proposed.

Research progression of PD-1/PD-L1 in non-small cell lung cancer

Lung cancer is the leading cause of cancer-related mortality worldwide. Despite great progress in the development of target agents, most people who do not harbor a mutation do not benefit from these agents. Immunotherapy, which stimulates the body's immune system to improve the anti-tumor immunity effect, is a new therapeutic method for non-small cell lung cancer(NSCLC). Programmed cell death 1(PD-1) and its ligand(PD-L1) belong to the CD28/B7 immunoglobulin super-family and are co-stimulatory molecules that show negative regulation effects. Combined with its ligand, PD-1 can modulate the tumor microenvironment, enabling tumor cells to escape host immune surveillance and elimination and play a key role in the clinical significance of NSCLC. An increasing number of clinical trials have suggested that immune checkpoint inhibitors, including anti-PD-1 and anti-PD-L1 monoclonal antibodies, are beneficial and safe for NSCLC. Here, we review the brief history of PD-L1 as a biomarker, mechanism of action, and critical role of PD-1/PD-L1 in the treatment of NSCLC as well as the current research status and future directions.

Targeting sphingosine-1-phosphate signaling for cancer therapy

Sphingosine-1-phosphate(S1P) is a potent pleotropic bioactive lipid mediator involved in immune cell trafficking, cell survival,cell proliferation, cell migration, angiogenesis and many other cellular processes. S1 P either activates S1 P receptors(S1PR1-5) through "inside-out signaling" or acts directly on intracellular targets to regulate various cellular processes. In the past two decades, much progress has been made in exploring S1 P signaling and its pathogenic roles in diseases as well as in developing modulators of S1 P signaling, including S1 P agonists, S1 P antagonists and sphingosine kinase(SphK) inhibitors.Ceramide and S1 P have been defined as reciprocal regulators of cell fate, and S1 P signaling has been shown to be crucial for the pathogenesis of various diseases, including autoimmune diseases, inflammation and cancer; therefore, targeting S1 P signaling may curtail the process of pathogenesis and serve as a potential therapeutic target for the treatment of these diseases. In this review, we describe recent advances in our understanding of S1 P signaling in cancer development(particularly in inflammationassociated cancer) as well as in innate and adaptive immunity, and we also discuss modulators of S1 P signaling in cancer treatment.