2025年 · 第03卷第04期

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.

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

Background: 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). Methods: 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. Results: 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. Conclusions: 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.

Background: 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. Methods: 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). Results: 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. Conclusions: Camrelizumab combined with L. paracasei showed favorable anticancer activity and may be a viable second-line treatment for patients with ESCC.