Frontiers in Oncology最新文献

Pancreatic ductal adenocarcinoma (PDAC) is the most aggressive and invasive type of pancreatic cancer and is expected to soon become the second leading cause of cancer-associated death. The high mortality rate is due to the clinical features that allow asymptomatic progression to advanced stages, a period when current therapeutic treatments have limited efficacy. To address these challenges, researchers are focused on identifying new molecular and circulating markers for early PDAC detection and precision medicine. In this mini-review, we report the most well-known and recently identified molecular and circulating biomarkers. This study aimed to emphasize the need for continued innovative research to develop diagnostic algorithms and therapies to improve the management of patients with PDAC.

In the management of advanced non-squamous non-small cell lung cancer (NSCLC) without driver gene mutations, the current therapeutic strategies encompass chemotherapy, chemotherapy combined with anti-angiogenic therapy, and chemotherapy combined with immunotherapy. For patients with high programmed death-ligand 1(PD-L1) expression, monotherapy with immune checkpoint inhibitors is a viable option. Recognizing that some patients cannot tolerate or decline chemotherapy, clinical practice has introduced non-chemotherapeutic treatment regimens, which have shown promising results. This article presents a clinical case of advanced NSCLC with low PD-L1 expression and negative driver gene mutations. The patient was treated with a chemotherapy-free regimen combining envafolimab with endostar. After 17 months of follow-up, both the primary tumor and metastatic lesions exhibited significant reduction, and no notable adverse reactions were observed. This case demonstrates the efficacy of envafolimab combined with endostar in the treatment of advanced NSCLC. This regimen enhances treatment safety and patient compliance, potentially offering a novel therapeutic option for patients with advanced NSCLC characterized by low PD-L1 expression and negative driver gene mutations.

Background: To explore new modulatory intervention targets for radiation-induced lung injury, bioinformatics analysis technology was used to search for the core driving genes in the pathogenesis of radiation pneumonitis, and the results were verified by a radiation-induced murine lung injury model to find possible new targets for the treatment of radiation lung injury.

Method: Gene Expression Omnibus Database was used to identify differentially expressed genes in radiation pneumonitis. DAVID database was used for gene ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) enrichment analysis. Gene Set Enrichment Analysis was used to analyze abnormal expressions. Protein-protein interaction networks were constructed using STRING and Cytoscape. Discovery Studio 4.5 software was used to find the preferred inhibitor of the specific gene. A radiation-induced lung injury model was induced in female C57BL/6N mice. The specific inhibitors were administered by intraperitoneal injection 24 h before and for 7 consecutive days after radiation. Lungs were harvested for further analysis 14 days and 10 weeks post-irradiation.

Results: We screened Syk as one of the most important driver genes of radiation pneumonitis by bioinformatics analysis and screened the preferred Syk inhibitor fostamatinib from the drug database. Syk was highly expressed in irradiated lung tissue, and fostamatinib inhibited the level of Syk expression. Syk inhibitor significantly alleviated the radiation-induced lung injury and downregulated the increased expression of p38 MAPK, p53, IL-1β, and IL-6 in lung tissue at 2 weeks after radiation. The levels of TGF-β, COL1A1, and α-SMA and degree of pulmonary fibrosis at 10 weeks after radiation were also decreased by Syk inhibitor.

Conclusion: Syk inhibitor may have a potential to be used as a targeted drug to mitigate radiation pneumonitis and inhibit radiation-induced pulmonary fibrosis.

Introduction: When elderly patients have underlying diseases combined with oromaxillofacial diseases requiring surgical treatment, the application of conventional general anesthesia (GA) for oromaxillofacial surgical diseases has become a risk due to underlying disease reasons. The objective of this study was to evaluate the efficacy and safety of ultrasound-guided superficial cervical plexus block (SCPB) anesthesia combined with local infiltration anesthesia (LIA) for partial oral and maxillofacial surgery (OMFS) in patients who with risk for GA due to underlying disease.

Methods: The clinical data of 7 high risk patients with OMFS treated with SCPB anesthesia combined with LIA were retrospectively analyzed. All seven surgeries were performed on one side of the neck. All patients were given ultrasound-guided SCPB anesthesia by the same anesthesiologist, LIA by the same surgeon, and surgery was performed under continuous Electrocardiogram (ECG) monitoring.

Results: Seven patients had stable vital signs and no significant postoperative complications. The results of this study indicated that SCPB anesthesia combined with LIA is a safe and effective anesthesia technique with a high success rate and patient tolerance.

Discussion: For patients with OMFS who have a risk for GA due to underlying diseases, ultrasound-guided cervical superficial plexus block anesthesia combined with LIA is a safe and effective alternative to conventional GA.

Tumor-associated macrophages (TAMs) play a pivotal role in sculpting the tumor microenvironment and influencing cancer progression, particularly through their interactions with various forms of regulated cell death (RCD), including apoptosis, pyroptosis, ferroptosis, and necroptosis. This review examines the interplay between TAMs and these RCD pathways, exploring the mechanisms through which they interact to promote tumor growth and advancement. We examine the underlying mechanisms of these intricate interactions, emphasizing their importance in cancer progression and treatment. Moreover, we present potential therapeutic strategies for targeting TAMs and manipulating RCD to enhance anti-tumor responses. These strategies encompass reprogramming TAMs, inhibiting their recruitment, and selectively eliminating them to enhance anti-tumor functions, alongside modulating RCD pathways to amplify immune responses. These insights offer a novel perspective on tumor biology and provide a foundation for the development of more efficacious cancer therapies.

Background: Non-small cell lung cancer (NSCLC) with human epidermal growth factor receptor 2 (HER2) alterations poses a substantial treatment challenge. Current HER2-targeted therapies offer limited efficacy. Antibody-drug conjugates (ADCs) targeting HER2 have emerged as a promising therapeutic strategy. This study aimed to evaluate the clinical response to a novel ADC drug Disitamab vedotin (RC48) in advanced NSCLC with HER2 alterations.

Methods: This study conducted a retrospective review of patients harboring HER2 alterations treated with RC48 in the real world. Clinical outcomes were evaluated in terms of objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS).

Results: Out of 22 patients, 21 (95.5%) received RC48 combination therapy, while one received RC48 monotherapy. The ORR of all patients reached 45.5%, and the DCR stood at 90.9%. The median PFS (mPFS) was 7.5 months. Among patients receiving RC48 combination therapy, the ORR was 47.7%, and the mPFS of 8.1 months. The combination of RC48 with platinum+/- bevacizumab resulted in the highest ORR of 71.4% (5 out of 7 patients), with HER2 TKI following at a 50.0% ORR (4 out of 8 patients). First-line (1L) treatment with RC48 showed an ORR of 62.5% (5 out of 8 patients), second-line (2L) treatments had a 57.1% ORR (4 out of 7 patients), and beyond second-line (>2L) treatments exhibited a 14.3% ORR (1 out of 7 patients). Patients with 1L, 2L, or >2L treatment had a mPFS of 8.1 months, 7.2 months, and 7.4 months, respectively. Patients with HER2 mutations or amplifications, and those with concurrent mutations and amplifications at baseline, showed mPFS of 8.1 months, 9.4 months, and 7.4 months, respectively. The mPFS was significantly longer in patients with HER2 amplification. The most common adverse events included hand-foot syndrome (54.5%), asthenia (50.0%), decreased white blood cell count (45.5%), and liver impairment (45.5%). Grade 3 adverse events occurred in one (4.5%) patient.

Conclusion: RC48, particularly in combination regimens, demonstrates promising efficacy in advanced NSCLC with HER2 alterations. These findings underscore the need for further research to validate RC48's application in clinical practice.

Purpose: We sought to develop and validate a nomogram for predicting extra-urinary recurrence (EUR) following radical nephroureterectomy (RNU) in patients with upper urinary tract urothelial carcinoma (UTUC).

Methods: Data from 556 UTUC patients post-RNU at the First Hospital of Jilin University were retrospectively analyzed. These patients were categorized into a training group (n=389) and a validation group (n=167). Variables significantly associated with prognosis were identified using univariate Cox regression and most minor absolute shrinkage and selection operator (LASSO) analysis. These independent predictors were incorporated into the nomogram to estimate extra-urinary recurrence-free survival (EURFS). Validation of the nomogram involved ROC curves, calibration plots, and decision curve analysis (DCA). Patients were stratified into two risk categories based on their nomogram scores to compare EURFS using the Kaplan-Meier method.

Results: Eight predictors were identified: T-stage, N-stage, tumor grade, local and nerve invasion, preoperative hemoglobin level, neutrophil-to-lymphocyte ratio (NLR), and creatinine, all proving to be independent predictors of EUR. A nomogram was created based on these eight factors, and using the ROC, calibration curves, and DCA, good prediction results were shown in both the training and validation groups. The training and validation groups also showed reliable predictive performance. In particular, there was a significant difference in survival between the high-risk and low-risk groups (P<0.0001). We have also built a network calculator that calculates patient survival time. The URL is https://haowu24.shinyapps.io/dynnomapp.

Conclusion: A nomogram for predicting distant metastases in UTUC patients was successfully developed, and its accuracy, reliability, and clinical value were demonstrated. This new tool helps to improve the clinical management of UTUC cases.

The discovery of gene fusions involving Neuregulin-1 (NRG1) within solid tumors has important therapeutic implications, as they are being actively explored as targets for emerging ERBB/ERBB2/ERBB3-directed anti-cancer agents. NRG1 fusions are very uncommon across all tumor types and are infrequently documented in the medical literature. We report a female patient presenting with widespread peritoneal carcinomatosis diagnosed as high grade serous fallopian tube carcinoma, which harbored a previously undescribed MYH10::NRG1 fusion. Moreover, we queried the whole transcriptome sequencing results of neoplasms analyzed by a commercial laboratory (Caris Life Sciences) to determine the overall incidence of NRG1 fusions in carcinomas of the ovary, fallopian tube, and peritoneum (0.18%). Twenty-five additional tumors were found to demonstrate NRG1 fusions, including 20 new genes partners that had not been previously identified in gynecologic carcinomas. Overall, NRG1 fusion events are rare in ovarian, fallopian tube, and primary peritoneal carcinomas, but they may carry diagnostic significance in the context of borderline/low grade serous tumors, which demonstrated exclusively CLU::NRG1 fusions, and could have important predictive implications for response to ERBB/ERBB2/ERBB3-directed therapies.

Cervical cancer is a common malignant tumor of female reproductive system. Radiation therapy is one of the main methods of cervical cancer treatment, of which brachytherapy is an essential and important part of radiation therapy for locally advanced cervical cancer. With the rapid development of imaging technologies such as computed tomography (CT) and magnetic resonance imaging (MRI), brachytherapy for cervical cancer has gradually developed from traditional two-dimensional image-guided technology to three-dimensional image-guided technology. And there are more and more treatment methods, including intracavitary brachytherapy, interstitial brachytherapy, and intracavitary combined interstitial implantation brachytherapy. We performed a PubMed search for introduce the application progress of intracavity, implantation, intracavity combined implantation brachytherapy and radioactive seed implantation, and discuss the dosimetric feasibility of internal and external fusion irradiation.