2025年 · 第03卷第04期

超重和肥胖通常使用体重指数(BMI)来测量，超重被归类为BMI为25-29.9 kg/m²BMI≥30 kg/m的肥胖²和BMI≥40kg/m的病态肥胖².¹超重和肥胖是重大健康危机，对当前全球健康进步构成威胁。²2021年，371万人死亡和1.29亿人残疾调整生命年(DALY)归因于超重和肥胖。³随着全球儿童和青少年肥胖率的持续飙升，预计成人肥胖率将会上升。因此，各种非传染性疾病（NCD）的负担——特别是糖尿病、心血管疾病和癌症——将继续升级。⁴预计到2070年，全球与肥胖相关的癌症病例数也将上升至>200万新病例，占所有癌症的7%。⁵越来越多的证据表明，体重管理不仅影响代谢性疾病，还影响癌症的发展、进展和治疗结果。我们旨在讨论最近的研究，以探索体重变化与癌症发病机制和治疗之间的多维关系。

形态学、免疫学、细胞遗传学、分子生物学（MICM）诊断系统已成为血液病诊疗领域的行业标准。¹随着分子生物学和基因组学技术的快速发展，血液肿瘤的分子诊断和治疗取得了显著进展，为患者提供了更加精准有效的治疗策略。该特刊名为“血液癌症中的精准医学”，重点关注血液恶性肿瘤治疗中的众多挑战，包括耐药性、不良事件和疾病复发，并探索整合最新分子检测的方法，以提高诊断准确性和治疗安全性。

这期特刊名为“泌尿肿瘤学的基础和转化研究”，致力于泌尿肿瘤学临床、基础和转化研究的最新进展。近年来，泌尿系统肿瘤，特别是前列腺癌（PCa）的发病率一直在急剧增加，现在是男性中第二大流行癌症。¹本期的文章涵盖了广泛的主题，从长非编码核糖核酸（lncRNAs）在前列腺癌发病机制中的新兴作用到三维（3D）增强现实在机器人辅助根治性前列腺切除术中的集成。每一篇文章都提供了有价值的见解，增强了我们对泌尿系统癌症的理解、诊断和治疗，特别强调前列腺癌。

This consensus on multiple myeloma-related bone diseases (MBDs) underscores the importance of a multidisciplinary approach that encompasses hematology, radiology, orthopedics, and additional specialties to tackle its intricate challenges. MBD, a prevalent and debilitating complication of multiple myeloma, leads to bone pain, fractures, and skeletal-related events (SREs), which profoundly impact patients’ quality of life. The guidelines offer a thorough framework for diagnosis, treatment, and continual assessment, emphasizing early detection and consistent monitoring using imaging techniques such as positron emission tomography-computed tomography (PET-CT) and magnetic resonance imaging (MRI). Treatment strategies prioritize the careful application of antimyeloma agents, bisphosphonates, and denosumab to minimize bone loss and decrease SRE risk, complemented by surgical and radiotherapy interventions for structural or pain-related issues. Supportive care measures, including pain management, rehabilitation, nutritional support, and dental evaluations, play a crucial role in enhancing patient outcomes and preserving quality of life. This consensus advocates a standardized, evidence-based approach to managing MBD, ensuring comprehensive and coordinated care for patients.

One in six deaths worldwide is caused by cancer, making it a major global health concern. Despite their effectiveness, traditional treatment approaches such as radiation therapy, chemotherapy, and surgery frequently have negative side effects and high costs. New approaches, such as gene therapy, are promising but are hampered by high costs and accessibility problems. Nanoparticles (NPs) facilitate targeted drug delivery by leveraging passive targeting mechanisms, such as the enhanced permeability and retention (EPR) effect, and by actively targeting surfaces with ligands for site-specific binding through the functionalization of surfaces. This approach enhances therapeutic results while lowering off-target toxicities. Notably, chemotherapeutic medications, immunotherapeutic agents, and photothermal therapies can now be delivered more precisely to the affected site using NP-based systems. By boosting particularity, reducing side effects, and tackling drug resistance, nanomedicine has the potential to revolutionize cancer treatment and ultimately advance personalized oncological care. These advancements highlight the possibilities for field growth, and future development regulations are detailed.

Circular ribonucleic acid (circRNA) vaccines have emerged as a revolutionary strategy in cancer immunotherapy, facilitating novel approaches to induce robust and durable immune responses. Unlike traditional linear messenger RNA (mRNA) vaccines, circRNAs exhibit exceptional stability, enhanced translational efficiency, and resistance to exonuclease degradation, making them ideal candidates for vaccine development. This review delved into the fundamental principles underlying circRNA biology, highlighting their unique structural advantages and translational potential. We examined recent advancements in circRNA vaccine design, focusing on their application in oncology. As the circRNA-based cancer vaccine is a relatively novel technology, findings from all the major studies describing its efficacy were discussed. We further investigated their combination with other immunotherapeutic modalities, such as immune checkpoint inhibitors and adoptive cell therapies, that ensure the maximal anticancer effects of circRNA vaccines. Large-scale manufacturing, immunogenicity optimization, delivery systems, and other challenges and future directions in this field were also discussed. This study aims to thoroughly analyze the state-of-the-art and potential future applications of circRNA vaccines in cancer immunotherapy, highlighting them as exciting possibilities for next-generation cancer therapies.

Cancer therapy has undergone significant advances in recent decades attributed to personalized medicine and targeted drug delivery. Among the promising approaches, the use of nano-based delivery systems has become a relevant approach capable of improving treatment by releasing antineoplastic drugs at the target site, improving therapeutic efficacy, minimizing cytotoxicity in healthy tissues, and ultimately, reducing the intensity of adverse effects of chemotherapy. This study prospectively evaluated the impact of formulating antineoplastic drugs as nanomedicines on clinical response, overall survival, safety, and quality of life of cancer patients, based on the outcomes of randomized clinical trials.

A literature review was carried out by systematically searching the PubMed/MEDical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica Database (EMBASE), and Latin American and Caribbean Health Sciences Literature (LILACS) databases for phase III clinical trials, comparing nanomedicines with conventional therapies for the treatment of various cancer types.

The nanomedicines analyzed were those that are approved and used in Brazil, considering the country's emerging market for advanced cancer treatments. From a total of 303 articles found, 26 articles were selected for systematic review. Studies showed that PEGylated _L-asparaginase achieved a similar therapeutic effect to that of _L-asparaginase, with fewer applications due to its longer half-life. Paclitaxel bound to albumin improved therapeutic efficacy as well as reduced infusion time and solvent-related toxicity of the conventional paclitaxel formulation. PEGylated liposomal doxorubicin showed better pharmacokinetics, reduced cardiotoxicity, and improved quality of life in cancer patients compared to that of free doxorubicin.

This study reinforces the scientific evidence of the added value of nanomedicines to improve therapeutic efficacy and reduce toxicity in patients under chemotherapy.

SIBP04 is a biosimilar of bevacizumab (Avastin^®, Roche, Basel, Switzerland). This study evaluated the equivalence of SIBP04 to Avastin^® as first-line treatment for locally advanced or metastatic non-squamous non-small-cell lung cancer (nsqNSCLC).

In this randomized, double-blind, multi-center, phase 3 trial, we recruited patients with locally advanced or metastatic nsqNSCLC from 58 hospitals at China. Patients were randomly allocated 1:1 to receive SIBP04 or Avastin^® (15 mg/kg) combined with paclitaxel (175 mg/m²) and carboplatin (area under curve [AUC] =5.0, no more than 800 mg) (PC) regimens intravenously (3-week cycles, up to six cycles) followed by SIBP04 maintenance therapy. The primary endpoint was objective response rate (ORR), defined as the best overall response from the first dose to the 18th week, assessed by the independent review committee (IRC) according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Clinical equivalence of the primary endpoint was done by comparing the two-sided 90% confidence interval (CI) of the ORR ratio (SIBP04 plus PC vs. Avastin^® plus PC) in the per-protocol set (PPS) populaiton with the prespecified equivalence margin of 0.75–1.33. Secondary endpoints included progression-free survival, overall survival, duration of response, disease control rate, safety, immunogenicity, and pharmacological bioequivalence of steady-state trough concentrations.

From April 17, 2020, to April 20, 2021, 517 patients were randomly assigned to receive SIBP04 plus PC (n =259) or Avastin^® plus PC (n =258). The ORR of the SIBP04 plus PC group was 55.6% (95% CI, 49.3–61.8) and that of the Avastin^® plus PC group was 59.3% (95% CI, 53.0–65.4) in the full analysis set (FAS) population (P=0. 3944). The ORR of the SIBP04 plus PC group was 62.6% (95% CI, 55.8–69.0) and that of the Avastin^® plus PC group was 64.7% (95% CI, 58.0–71.0) in the PPS population (P =0.6448). The ORR ratio (SIBP04 plus PC vs. Avastin^® plus PC) was 0.94 (90% CI, 0.8270–1.0621) in the FAS population and 0.97 (90% CI, 0.8578–1.0900) in the PPS population, respectively, both within the prespecified equivalence margin of 0.75–1.33. Other efficacy endpoints, safety, immunogenicity, and pharmacokinetics were all comparable across the groups.

SIBP04 showed equivalent efficacy and safety profile to Avastin^® in patients with locally advanced or metastatic nsqNSCLC. SIBP04 plus PC regimen will offer an alternative first-line treatment option for this patient population.

Esophageal cancer (EC) is the seventh most prevalent cancer and the sixth most common cause of cancer-related mortalities worldwide. Camrelizumab, a monoclonal antibody, has demonstrated moderate efficacy in esophageal squamous cell carcinoma (ESCC). Lactobacillus paracasei, a probiotic bacterium, has a complementary effect in immunotherapy. This study aimed to evaluate the combination of camrelizumab and L. paracasei for advanced ESCC.

This single-arm, single-center, exploratory trial was conducted at the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. Eligible patients received 200 mg camrelizumab biweekly and two bags of L. paracasei twice daily. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were disease control rate (DCR), overall survival (OS), objective response rate (ORR), and adverse events (AEs).

From May 2020 to October 2022, ten patients with advanced ESCC who did not respond to first-line therapy were admitted. At the data cutoff date (August 9, 2023), the median follow-up duration was 12 months. Two of 10 (20%) achieved objective responses. The median survival was 7.5 months and the median OS was not reached. Grade 3 treatment-related AEs occurred in two of the 10 patients (20%). No serious treatmentrelated AEs or deaths occurred.

Camrelizumab combined with L. paracasei showed favorable anticancer activity and may be a viable second-line treatment for patients with ESCC.

在精准肿瘤学时代，来自癌症患者的肿瘤活检或血浆（也称为液体活检）的分子图谱在指导治疗选择方面至关重要。液体活检允许鉴定可药用生物标志物，促进最佳癌症护理管理。¹由于目前批准用于指导靶向治疗的多种遗传生物标志物，非小细胞肺癌（NSCLC）处于最前沿。间充质上皮转化(MET)是一种具有多效性功能的受体酪氨酸激酶，例如启动和维持肿瘤转化，驱动癌症克隆进化，以及在治疗开始后和在治疗压力下向转移的进展。²外显子14跳跃（METex14跳跃）和扩增（METamp）是两个重要的MET具有不同致癌作用的非小细胞肺癌的失调。这两者的同时存在MET非小细胞肺癌患者的改变很少被报道，其对患者对MET抑制剂（如capmatinib）反应的集体影响的知识仍然难以捉摸。在本文中，我们报告了一例被诊断为肺腺癌和脑转移的60岁女性患者，该患者在一线（1L）osimertinib治疗中进展为新的肝转移，以及后续检测和治疗管理的结果。