Critical reviews in oncology/hematology最新文献

Neuroblastoma (NB) is the most common extracranial solid tumor in children, with variable outcomes ranging from spontaneous remission to high-risk cases often leading to relapse or refractory disease. Approximately 50 % of patients with NB have high-risk features, often experiencing relapse or refractory disease despite intensive treatments and the prognosis remains poor, with long-term event-free survival (EFS) rates below 10 %,Radioactive iodine-labeled meta-iodobenzylguanidine (¹³¹I-mIBG) therapy, leveraging NB cells' radiosensitivity and expression of the norepinephrine transporter (NET), has shown promise in treating relapsed or refractory NB. Since 1985, ¹³¹I-mIBG has been studied to determine the maximum tolerated dose and side effects, with recent trials exploring its use in front-line treatment. Our systematic review, based on MEDLINE, EMBASE, and Cochrane CENTRAL databases up to December 2023, evaluates the effectiveness and toxicity of ¹³¹I-mIBG therapy in relapsed/refractory NB. It also discusses its potential role in conjunction with emerging therapies like CAR-T cells, haploidentical stem cell transplantation, and dinutuximab beta.

Pancreatic cancer, especially pancreatic ductal adenocarcinoma (PDAC), is one of the most challenging clinical conditions due to its late-stage diagnosis and poor survival rates. Mesenchymal stem cells (MSCs), used for targeted therapies, are being explored as a promising treatment because of their tumor-homing properties and potential contributions to the pancreatic cancer microenvironment. Understanding these interactions is crucial for developing effective treatments. In this study, we investigated how MSCs exhibit tropism towards tumors, influence the microenvironment through paracrine effects, and serve as potential drug delivery vehicles. We also examined their role in progression and therapeutic resistance in pancreatic cancer therapy. The cytotoxic effects of certain compounds on tumor cells, the use of genetically modified MSCs as drug carriers, and the potential of exosomal biomarkers like miRNAs and riRNAs for diagnosis and monitoring of pancreatic cancer were analyzed. Overall, MSC-based therapies, coupled with insights into tumor-stromal interactions, offer new avenues for improving outcomes in pancreatic cancer treatment. Additionally, the use of MSC-based therapies in clinical trials is discussed. While MSCs show promising potential for pancreatic cancer monitoring, diagnosis, and treatment, results so far have been limited.

In recent years, cancer immunotherapy has received widespread attention due to significant tumor clearance in some malignancies. Various immunotherapy approaches, including vaccines, immune checkpoint inhibitors, oncolytic virotherapy, bispecific T cell engagers, and adoptive T cell transfer, have completed or are undergoing clinical trials for prostate cancer. Despite immune checkpoint blockade's extraordinary effectiveness in treating a variety of cancers, targeted prostate cancer treatment using the immune system is still in its infancy. Multiple factors including the heterogeneity of prostate cancer, the cold tumor microenvironment, and a low level of neoantigens, contribute to the poor immunotherapy response. Significant effort is being devoted to improving immune-based prostate cancer therapy. Recently, several key discoveries demonstrate that prostate cancer immunotherapy agents may be used to promise better prognosis for patients as part of combination strategies with other agents targeting tumor-associated immune mechanism of resistance. Here, this review comprehensively examines the recent advancements in immunotherapy for prostate cancer, exploring its potential synergistic effects when combined with other treatment modalities to enhance clinical efficacy.

High-grade serous ovarian carcinoma (HGSOC) is the most aggressive subtype of epithelial ovarian cancer and a leading cause of mortality among gynecologic malignancies. This review aims to comprehensively analyze the morphological, immunohistochemical, and molecular features of HGSOC, highlighting its pathogenesis and identifying biomarkers with diagnostic, prognostic, and therapeutic significance. Special emphasis is placed on the role of tumor microenvironment (TME) and genomic instability in shaping the tumor's behavior and therapeutic vulnerabilities. Key advancements, such as the identification of TP53 and BRCA mutations, the classification of homologous recombination repair (HRR) deficiencies, and the clinical implications of biomarkers like folate receptor alpha (FRα) and PD-L1 are discussed. These findings reveal actionable insights into targeted therapies, including immune checkpoint inhibitors and PARP inhibitors, which hold promise for improving outcomes in HGSOC. This synthesis of knowledge aims to bridge gaps in understanding HGSOC's multifaceted biology, enhance clinical decision-making, and foster the development of precision therapies.

Lymph node metastasis (LNM) significantly affects the prognosis and clinical management of breast cancer (BC) patients. This systematic review and meta-analysis aim to identify microRNAs (miRNAs) associated with LNM in BC and evaluate their potential diagnostic and prognostic value. Following PRISMA guidelines, a comprehensive literature search was conducted in PubMed, Web of Science, and SCOPUS databases, to assess the role of miRNAs in LNM BC. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool was used to evaluate the quality of included studies. A total of 84 miRNAs were identified as differentially expressed in BC patients with LNM. Of these, a meta-analysis was performed in two microRNAs that were present in at least 3 different articles with a coherent expression direction: miR-155 and miR-34a. The meta-analysis returned a pooled a Log2 fold change of 1.50 for miR-155 (upregulated) and -0.53 for miR-34a (downregulated) with no evidence of publication bias, and a low risk of bias and applicability concerns. To conclude, this study names miR-155 and miR-34a as potential diagnostic biomarkers for LNM in BC, although further experimental validation is necessary to confirm these findings and develop non-invasive diagnostic tools for clinical use.

Background: To contribute to the refinement of future physical activity (PA) guidelines, which have remained mostly generic until now, we performed an umbrella review of meta-analyses for PA in cancer survivors.

Methods: Medline and Scopus databases were searched in January 2024 for systematic reviews and meta-analyses on the association/effect of any type of PA in every cancer type and for any studied outcome. Statistically significant meta-analyses were categorized into four evidence groups (strong, highly suggestive, suggestive, weak) using pre-established grading criteria.

Results: A total of 102 publications reporting 740 meta-analytic associations were identified, including breast (n = 427), prostate (n = 104), hematological (n = 58), colorectal (n = 79) and lung (n = 54) cancer survivors. Overall, 401 (54 %) associations were nominally statistically significant, of which 16 were categorised as strong, 10 as highly suggestive, and 93 as suggestive evidence. In breast cancer, there was strong or highly suggestive evidence that post-diagnosis PA is associated with lower all-cause mortality, recurrence, cancer-related fatigue, depression, and higher mental health, body strength, aerobic capacity, and weight loss. In prostate cancer, strong evidence was identified for the positive association of PA with cardiovascular fitness, quality of life and fatigue amelioration. In colorectal cancer, strong and highly suggestive evidence supported the association of PA with lower all-cause mortality. In lung cancer, strong evidence supported the association of preoperative combination of breathing exercise and PA with reduced length of hospital stay.

Conclusion: This grading of the entirety of the available evidence can facilitate robust introduction of targeted exercise prescription in oncology care as standard practice.

Liver transplantation (LT) is a curative strategy for hepatocellular carcinoma (HCC), but the risk of HCC recurrence remains a challenging problem. In patients with HCC recurrence after LT (HCC-R_LT), the locoregional and surgical approaches are complex, and the guidelines do not report evidence-based strategies for the management of immunosuppression. In recent years, immunotherapy has become an effective option for patients with advanced HCC in pre-transplant settings. However, due to the risk of potentially fatal allograft rejection, the use of immunotherapy is avoided in post-transplant settings. Combining immunosuppressants with immunotherapy in transplant patients is also challenging due to the complex tumor microenvironment and immunoreactivity. The fear of acute liver rejection and the lack of predictive factors hinder the successful clinical application of immunotherapy for post-liver transplantation HCC recurrence. This review aims to comprehensively summarize the risk of HCC-R_LT, the available evidence for the efficacy of immunotherapy in patients with HCC-R_LT, and the clinical issues regarding the innovative management of this patient population.

Prostate cancer (PCa) is highly prevalent among aging men and a significant contributor to global mortality. Balancing early detection and treatment of "clinically significant" disease with avoiding over-detection and overtreatment of slow-growing tumors is challenging, especially for elderly patients with competing health risks and potentially aggressive disease phenotypes. This review emphasizes the importance of individualized approaches for diagnosing and treating PCa in geriatric patients. Active surveillance and watchful waiting are common strategies, while surgical interventions are less frequent but considered based on comorbidities, disease risk, and patient preferences. Radiotherapy, often combined with androgen deprivation therapy, is typical for higher-risk cases, and focal therapy is emerging to reduce morbidity. An inclusive approach combining advanced diagnostics, life expectancy considerations, and minimally invasive interventions can improve decision-making. Integrating multidisciplinary strategies with better risk stratification and less invasive options can significantly enhance care and outcomes for elderly patients with significant PCa.

Background: Immune-related adverse events (irAE) pose challenges to the use of immune checkpoint inhibitors (ICI). While risk factors for irAE are emerging, most studies are small, retrospective analyses that seldom report on diverse cancers or rare irAE. This paper reports a systematic review that summarises literature on irAE risk factors across cancers and proposes a categorisation approach.

Method: A systematic search was conducted in Medline OVID, Embase and Web of Science databases following PRISMA guidelines (CRD42022310127). Original research published in peer-reviewed journals between January 2017-Decmeber 2021 were selected. Eligible studies included patients with any cancer and evaluated any potential risk factor for any grade/type of irAE. Study design, sample size, and method for analysing association between irAE and risk factors were compared.

Results: A total of 293 eligible studies containing 305,879 patients receiving ICI reported irAE in 58,291 patients (19.1 %). There were 221 retrospective, 55 prospective studies, and 17 systematic reviews/meta-analyses. Eighteen studies evaluated the predictive validity of models. Proposed risk factors were grouped based on common themes and underlying aetiology: 1) patient, 2) laboratory, 3) medical history, 4) cancer-related, 5) clinical score, 6) medications, and 7) imaging features. Opposing associations were reported between advancing age and irAE risk.

Conclusion: This systematic review provides a comprehensive overview of evidence on irAE risk factors across a large patient population. Studies were heterogeneous resulting from variations in design, sample size and analysis method, and lack generalisability due to statistically underpowered evidence. We propose an approach to categorise potential irAE risk factors to support ongoing collaborative research.

Alternative polyadenylation (APA) serves as a crucial mechanism for the posttranscriptional regulation of gene expression and influences gene expression by generating diverse mRNA isoforms. This process is regulated by a diverse array of RNA-binding proteins (RBPs), which selectively bind to specific sequences or structures within the pre-mRNA molecule. Dysregulation of APA and its associated RBPs has been implicated in numerous diseases, including cardiovascular diseases, nervous system disease, and cancer. For instance, aberrant APA events have been observed in several types of tumors, contributing to tumor heterogeneity and affecting key cellular pathways involved in cell proliferation, invasion, metastasis, and response to therapy. This review critically evaluates the current understanding of APA mechanisms and the multifaceted roles of RBPs in orchestrating this intricate process. We highlight recent advancements in high-throughput sequencing and bioinformatics tools that have enhanced our ability to study APA on a genome-wide scale. Moreover, we explored the pathological consequences of APA dysregulation, emphasizing its role in oncogenesis. By elucidating the intricate relationships between APA and RBPs, this review aims to underscore the potential of targeting the APA machinery and RBPs for therapeutic intervention. Understanding these molecular processes holds promise for developing novel diagnostic markers and treatment strategies for a range of human cancers.