This study aimed to explore whether the combination of anlotinib and immunotherapy is an effective and safe alternative to chemotherapy for clinical treatment. Provide a new treatment plan for elderly patients who are unwilling to undergo chemotherapy, intolerant to chemotherapy, or have poor ECOG PS scores. This is a single-center retrospective investigation that collected clinical data of 58 elderly aNSCLC patients treated with anlotinib monotherapy or anlotinib plus PD-1/PD-L1 inhibitor combination therapy at Nanjing Chest Hospital during the period from January 1, 2020 to December 31, 2023, with the study being subject to a limited sample size. Fifty-eight elderly patients were evaluated after two cycles of anlotinib monotherapy and combined therapy. In the monotherapy group of 28 patients, the ORR and DCR were 25.0% (7/28) and 78.6% (22/28), respectively. Besides, the mPFS and the mOS reached up to 5.4 months (95% CI, 4.4-6.4 months) and 11.2 months (95% CI, 7.2-15.2 months), respectively. In the group with combination therapy of 30cases, the ORR for this group was calculated at 30.0% (9/30), the DCR was higher, at 86.7% (26/30), the mPFS and the mOS were determined to be 8.5 months (95% CI, 7.3-9.7 months) and 17.8 months (95% CI, 13.2-22.4 months), respectively. In multivariate COX analysis, brain metastasis and treatment methods were found to be independent risk factors for PFS alongside OS. Both groups had a comparable overall incidence of adverse events (AEs), at 70.0% and 64.3% respectively, with no statistically significant difference noted in the rate of grade 3 and above adverse events (23.3% versus 17.9%). Anlotinib combined with immunotherapy demonstrated superior efficacy and better tolerability than anlotinib alone. The combination of anlotinib and immunotherapy may provide a "chemo-free" treatment mode for elderly patients with non-small cell lung cancer who refuse or cannot tolerate chemotherapy and have poor ECOG PS scores.
Colorectal cancer (CRC) is the second leading cause of cancer-related mortality worldwide and the third most frequently diagnosed malignancy. Circulating microRNAs, particularly miRNA-92a, have gained prominence as non-invasive biomarkers due to their stability in biological fluids and disease-specific expression patterns. This study evaluates the diagnostic performance of circulating miRNA-92a for non-invasive colorectal cancer detection, both as an individual biomarker and in combination with other circulating miRNAs, including markers that are either members of the miRNA-92a family or unrelated miRNA candidates. This review was registered in PROSPERO (CRD420251070402). A systematic search of PubMed, ScienceDirect, and Google Scholar was conducted for articles published up to May 2025 in accordance with PRISMA guidelines. Eligible articles evaluated circulating miRNA92a for CRC diagnosis, used appropriate reference standards, and reported extractable sensitivity and specificity data. A bivariate random-effects model in STATA/BE v18.0 was used to generate pooled estimates of sensitivity, specificity, PLR, NLR, logDOR, and AUC. Study quality was assessed using QUADAS-2, and publication bias was examined with Deeks' funnel plot asymmetry test. Twenty-two studies from sixteen articles, involving 1918 CRC patients and 1446 healthy controls, were included. Circulating miRNA-92a and miRNA-92a-related circulating panels demonstrated pooled sensitivity and specificity of 86% and 91%. Overall diagnostic performance was high, with an AUC of 0.87. The logDOR was 3.71, with a pooled PLR of 18.54 and an NLR of 0.38. Subgroup analyses showed comparable accuracy between singlemarker and panel-based assays, and serum samples yielded more consistent results. QUADAS-2 indicated acceptable methodological quality, and no significant publication bias was detected (p = 0.06). Circulating miRNA-92a demonstrates superior diagnostic performance and considerable potential as a non-invasive biomarker for early CRC detection. Further large-scale prospective studies are required to standardize testing protocols and confirm their clinical applicability.
This study investigated the effects of ALO on apoptosis and ferroptosis in colorectal cancer HCT116 and SW480 cells and the underlying mechanisms. Cells were treated with varying ALO concentrations. CCK-8 assay assessed proliferation. Flow cytometry detected apoptosis. Lipid peroxidation was measured by BODIPY 581/591 C11 dye oxidation and TBA method. GSH content was determined by DTNB method. ROS and intracellular iron levels were assessed using fluorescent probes and iron assays. Molecular docking analyzed ALO-Nrf2 binding. Immunofluorescence detected Nrf2 expression. Western blot quantified apoptosis-related proteins (Bax, Bcl-2) and ferroptosis-related proteins (Nrf2, GPX4, xCT, DMT1). Effects of Nrf2 overexpression on ALO-treated cells were observed. ALO inhibited cell viability and increased apoptosis dose-dependently. It elevated lipid peroxidation and intracellular iron while reducing GSH. Ferroptosis inhibitors DFO and Fer-1 reversed cell death and reduced apoptosis. ALO induced ROS production, upregulated Bax/Caspase3, and downregulated Bcl-2. Molecular docking suggested ALO binds to Nrf2 via hydrogen bonding. Immunofluorescence and Western blot showed ALO suppressed Nrf2, GPX4, xCT, and DMT1 expression concentration-dependently. Nrf2 overexpression significantly attenuated ALO's inhibitory effects on proliferation and its induction of ferroptosis and apoptosis. ALO suppresses colorectal cancer cell proliferation by inducing apoptosis and ferroptosis via inhibition of the Nrf2 signaling pathway. Colorectal cancer is a leading global health problem, and new therapeutic strategies are urgently needed. This study investigated the inhibitory effects of ALO on colorectal cancer cells and the underlying molecular mechanisms. We treated two colorectal cancer cell lines (HCT116 and SW480) with different concentrations of ALO. ALO inhibited cancer cell proliferation in a dose-dependent manner by inducing two forms of cell death: apoptosis (programmed cell death) and ferroptosis (iron-dependent cell death). ALO increased reactive oxygen species (ROS) and lipid peroxidation, reduced the antioxidant GSH level, and elevated intracellular iron content. At the molecular level, ALO binds to and inhibits the key protein Nrf2, which is critical for cellular stress defense. This inhibition downregulated proteins that protect against ferroptosis. Overexpression of Nrf2 significantly reversed the effects of ALO, confirming its key role in the mechanism. Our findings demonstrate that ALO induces apoptosis and ferroptosis in colorectal cancer cells by suppressing the Nrf2 pathway, suggesting its potential as a promising candidate for colorectal cancer treatment. This study provides a novel strategy for developing more effective anti-cancer therapies.
For many patients with diffuse large B-cell lymphoma (DLBCL), frontline chemoimmunotherapy is curative; nonetheless, up to 40% of patients develop relapse or refractory disease. Immunotherapeutic approaches, such as immunomodulatory drugs, bispecific antibodies and chimeric antigen receptor T-cell therapy, have improved outcomes for relapsed/refractory DLBCL over the past ten years. However, treatment failure is still frequent because of tumor antigen loss, T-cell dysfunction, and an immunosuppressive tumor microenvironment (TME). DLBCL is a highly metabolically active cancer that impairs efficient anti-tumor immune responses by depleting vital nutrients and producing immunosuppressive metabolites such lactate, adenosine, and kynurenine. Targeting metabolic checkpoints, such as glutamine metabolism, indoleamine 2,3-dioxygenase, adenosine signaling, and lactate transport, may remodel the TME and improve the effectiveness of immunotherapy, according to new research. The immune metabolic interaction that restricts long-lasting responses is the main topic of this study, which summarizes current immunotherapeutic strategies in DLBCL. To improve T-cell fitness and overcome immunotherapy resistance, we critically assessed the preclinical and early clinical data supporting metabolic checkpoint inhibition. We also emphasize translational issues and potential future paths for logical combination treatments. Importantly, this review distinguishes itself from existing literature by specifically focusing on the integration of metabolic checkpoint inhibition with established immunotherapies in DLBCL, an area that remains underexplored. While preclinical data are promising, clinical evidence for many metabolic checkpoint inhibitors in DLBCL remains limited, and further prospective clinical studies are required to validate their therapeutic potential.
Head and neck squamous cell carcinoma (HNSCC) is characterized by a highly immunosuppressive tumor microenvironment (TME), with tumor-associated macrophages (TAMs) playing a central role in resistance to therapy. The immune checkpoint molecule CD47, known for its "don't eat me" signal, and EphA3, a receptor tyrosine kinase, are both upregulated in radiation-resistant HNSCC. However, their cooperative role in regulating TAMs and therapeutic resistance remains poorly understood. We established a radiation-resistant HNSCC model (MOC2R) using repeated irradiation and confirmed increased expression of CD47 and EphA3 in these cells. The effects of single and dual blockade of CD47 and EphA3 were evaluated through in vitro phagocytosis assays, Western blot, co-immunoprecipitation, and in vivo tumor models. Transcriptomic analysis and immunofluorescence staining were performed to elucidate molecular pathways involved in TAM modulation. We demonstrated in three independent experiments (n = 3) with statistical significance (P < 0.05). CD47 and EphA3 were upregulated in radioresistant HNSCC and recurrent tumors. Dual blockade synergistically enhanced macrophage-mediated phagocytosis (P < 0.01) and significantly reduced clonogenic tumor cell survival compared to single blockade (P < 0.0001). EphA3 inhibition reprogrammed tumor-associated macrophages toward an M1-like phenotype, with increased expression of pro-inflammatory markers and decreased M2-associated markers. In vivo, combination therapy significantly reduced tumor volume and weight and increased M1 macrophage infiltration, while reducing M2 macrophages. Mechanistically, EphA3 regulated macrophage polarization via the β-catenin/FOSL2/ARID5A axis, enhancing the efficacy of CD47 blockade. Our findings demonstrate that EphA3, in cooperation with CD47, promotes an immunosuppressive TME by modulating β-catenin/FOSL2/ARID5A signaling in TAMs. Dual targeting of EphA3 and CD47 represents a promising strategy to reprogram macrophages and enhance anti-tumor immunity in radiation-resistant HNSCC.
The RecQ DNA helicase family member WRN is an important protein for maintaining genome stability. The concept of attention as a synthetic lethal target for MSI-H tumors has garnered significant attention in recent years. However, the role of WRN in cancer development, diagnosis, and prognosis has not yet been systematically evaluated at the pan-cancer level. On the basis of multiple public cancer databases, we employed bioinformatics techniques to systematically assess WRN expression, variation, and interaction pathways across various cancers, along with the impact of WRN expression on immune profiling, drug sensitivity, and treatment, as a diagnostic tool. Additionally, we used three cancer cell lines to evaluate the suppressor function of WRN inactivation. WRN is highly expressed in rapidly proliferating tissues and is dysregulated in a cancer-specific manner, particularly in tumors with hereditary DNA repair deficiencies and myeloid malignancies. WRN expression and variants are correlated with prognosis and immune activation potential in cancers. In digestive cancer and endometrial cancer with a high proportion of MSI-H tumors, WRN is positively associated with MSI/TMB signatures. Pharmacogenomic analyses revealed significant correlations between WRN expression levels and sensitivity to the DNA synthesis inhibitors PI3K, ALK, and IFG1R and other target agents and immunomodulators. In vitro validation using WRN inhibitors demonstrated potent suppression of malignant phenotypes (proliferation, clonogenicity, migration, invasion) in colorectal, endometrial, and ovarian cancer models. Our study suggests that WRN plays a role in cancer diagnosis and therapy, especially in cancers characterized by replicative stress or defective DNA damage repair, and that WRN can serve as a potential target for cancer immunotherapy or targeted therapies and as a prognostic marker for certain tumors.
Regorafenib is a standard second-line therapy for advanced hepatocellular carcinoma (HCC), but its efficacy as a monotherapy is limited. Combining regorafenib with immune checkpoint inhibitors (ICIs) may enhance antitumor activity through synergistic modulation of the tumor microenvironment. This study synthesizes real-world evidence from comparative cohorts by summarizing arm-level efficacy and safety outcomes reported for regorafenib plus ICIs and for regorafenib monotherapy. A systematic search of PubMed, Embase, The Cochrane Library, and Web of Science was conducted up to January 10, 2026, to identify comparative real-world studies. Outcomes were synthesized primarily at the arm level: ORR was pooled as a single-arm proportion, and mPFS/mOS were summarized using reported medians. Random-effects models and exploratory meta-regression were used to examine differences in pooled arm-level summaries across cohort types rather than within-study head-to-head comparative effect estimates. Six studies involving 921 patients were included. Because adjusted within-study comparative estimates were inconsistently reported, findings should be interpreted as non-comparative arm-level summaries. In arm-level pooling, cohorts receiving regorafenib plus ICIs had a higher pooled ORR (0.28, 95% CI: 0.23-0.32) than cohorts receiving regorafenib monotherapy (0.10, 95% CI: 0.06-0.14). The pooled mPFS summary was longer in the combination cohorts (7.34 months; 95% CI: 6.09-8.59) than in the monotherapy cohorts (3.97 months; 95% CI: 3.16-4.77). The pooled mOS summary was numerically longer with the combination (16.87 months) versus monotherapy (11.07 months). The incidence of grade ≥3 adverse events was broadly similar between cohort types. In this arm-level synthesis of real-world comparative cohorts, regorafenib plus ICIs was associated with numerically higher pooled response and longer pooled mPFS summaries than regorafenib monotherapy, while severe adverse event incidence appeared broadly similar across cohort types. Because these results are based on non-comparative pooled arm-level estimates and heterogeneous observational cohorts, they should be considered hypothesis-generating rather than definitive evidence of superiority. Prospective comparative trials and well-adjusted real-world analyses are needed to clarify comparative effectiveness and identify patients most likely to benefit. PROSPERO CRD 420261290236.
Hyperfractionated thoracic radiotherapy (RT) is a standard component of curative treatment for limited-stage small-cell lung cancer (LS-SCLC). While 45 Gy in 30 twice-daily fractions remains the most validated regimen, recent Phase II data suggest that dose-escalated RT using 60 Gy in 40 fractions may improve outcomes. However, real-world data on this intensified regimen remain scarce. We conducted a retrospective cohort study of LS-SCLC patients treated with 60 Gy in 40 twice-daily fractions and concurrent platinum-etoposide chemotherapy at two tertiary centers. Modern radiation techniques were employed. Key outcomes included overall survival (OS), progression-free survival (PFS), patterns of failure, and treatment-related toxicity. Thirteen patients were included in the analysis. The median age at diagnosis was 59 years; 61.5% were female. At a median follow-up of 15 months, the 2-year OS rate was 71.4%, and the median OS was 30.9 months. The overall response rate was 60%. Most failures were distant; only one local failure was observed. Acute grade ≥3 esophagitis occurred in 7.6%, and no patients experienced grade ≥2 pneumonitis. Hematologic toxicity, particularly neutropenia, was frequent but manageable. No treatment-related deaths occurred. In this cohort, delivery of dose-escalated twice-daily thoracic radiotherapy using contemporary techniques was feasible and associated with acceptable toxicity in routine clinical practice. Survival outcomes were comparable to those reported in phase II studies of this approach. These findings warrant confirmation in larger, multi-institutional, or registry-based studies. Small-cell lung cancer is a fast-growing type of lung cancer that often spreads quickly. When it is found early and is still confined to one area of the chest, it is called “limited-stage” disease. In these cases, doctors treat patients with a combination of chemotherapy and radiation. A common approach is to give radiation twice a day for 3 weeks, which has been shown to help patients live longer. However, some recent studies suggest that giving a higher total dose of radiation over 4 weeks might work even better, without adding more side effects. In this study, we looked at 13 patients with small-cell lung cancer who were treated at two major hospitals. All patients received the higher radiation dose (60 Gy) twice a day, along with standard chemotherapy. We aimed to see how well this treatment worked in real-world settings and whether it was safe. We found that this treatment approach was generally well tolerated and showed promising results: most patients responded to the treatment, and serious side effects were uncommon. After 2 years, more than 70% of the patients were still alive, which is similar to results seen in clinical trials. Most cancer recurrences happened in other parts of the body, not in the thorax. These findings suggest that giving a higher dose of radiation twice a day is a practical and effective option for treating limited-stage small-cell lung cancer outside of clinical trials. This approach could help improve survival in some patients without causing more harm.
High-mobility group box 1 (HMGB1) is a ubiquitous non-histone nuclear protein with multifaceted roles in cancer biology. Emerging evidence suggests that the biological effects of HMGB1 are highly context-dependent, being determined by its subcellular localization, redox state, and release kinetics. Nuclear HMGB1 regulates chromatin structure and genome stability, whereas cytoplasmic HMGB1 controls autophagy and cell survival. When released extracellularly during cellular stress or therapy-induced immunogenic cell death, HMGB1 functions as a damage-associated molecular pattern that activates innate and adaptive immunity through pattern-recognition receptors such as Toll-like receptor 4. In this narrative review, we synthesize recent mechanistic and translational studies to clarify how HMGB1 regulates tumor proliferation, metastasis, and therapeutic responses under different treatment modalities. We particularly discuss the dual roles of HMGB1 in chemotherapy and emerging immunotherapies. Collectively, these insights highlight HMGB1 as a potential biomarker of treatment response and a therapeutically modifiable node for optimizing chemo-immunotherapy combination strategies.
Osteosarcoma (OS) is a highly malignant bone tumor primarily affecting children and adolescents. Clinical treatment has consistently encountered challenges, including chemotherapy resistance, high recurrence rates, and metastasis. Research has demonstrated that epigenetic regulation, particularly DNA methylation, can stably modify the DNA sequence without altering it, playing a key role in the development and progression of OS. Compared with normal tissue, OS exhibits distinctive alterations in DNA methylation, characterized by genome-wide hypomethylation and hypermethylation of specific gene promoter regions. This "dual pattern" not only promotes tumor proliferation, invasion, and metastasis but also maintains cancer stem cell characteristics and modulates the tumor immune microenvironment (TIME). Molecular classification based on DNA methylation profiles offers a new tool for the diagnosis and prognosis of OS. Drugs targeting DNA methylation, such as decitabine, have shown promising results for reversing gene silencing and suppressing tumor progression. This article systematically reviews the core mechanisms by which DNA methylation contributes to OS development, progression, and metastasis, and examines its potential for clinical translation.
Oncolytic virotherapy is a novel therapeutic approach in oncology that uses viruses to target and eradicate cancer cells specifically. To improve therapeutic effectiveness, we investigated the application of genetically modified oncolytic adenoviruses (OVs) engineered to express bispecific T-cell engager (BiTE) antibodies. In particular, we engineered Ad5-delta24 to express an EpCAM-targeting BiTE under the major late promoter, yielding the recombinant virus Ad5D24-Anti-EpCAM-Anti-CD3-scFv (rOAd5-BiTE). Following infection of A549 lung cancer cells, rOAd5-BiTE promoted the expression and secretion of BiTE antibodies targeting EpCAM and CD3. In co-culture experiments, rOAd5-BiTE elicited significant T-cell activation and proliferation, characterized by increased secretion of IFN-γ and IL-2, as well as augmented cytotoxic activity from neighboring bystander cells. Moreover, the combination of rOAd5-BiTE with peripheral blood mononuclear cells (PBMCs) markedly enhanced the antitumor activity against A549 cells. The results indicate that equipping OVs with BiTE molecules may address critical challenges in virotherapy by enhancing and redirecting T-cell activity within the tumor microenvironment. This strategy offers a promising avenue for developing targeted immunovirotherapy approaches for the treatment of solid tumors.
Immunotherapy in colorectal cancer (CRC) presents a striking dichotomy. MSS/pMMR tumors account for approximately 95% of metastatic CRC cases, representing a substantial global health burden. While immune checkpoint inhibitors (ICIs) have revolutionized treatment for mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) metastatic CRC-achieving durable responses in tumors with high mutational burden and a T-cell-inflamed microenvironment-the majority of microsatellite stable (MSS) cases remain resistant. The MSS tumor microenvironment is typically "cold", featuring low neoantigen load, poor T-cell infiltration, and dominant immunosuppressive networks. To overcome this resistance, extensive research is focused on combination strategies (ICIs with anti-angiogenic agents, targeted therapies, chemotherapy, radiotherapy) and next-generation modalities (adoptive cell therapies, bispecific antibodies, cancer vaccines). This review examines the biological basis for this dichotomy, summarizes clinical evidence in dMMR/MSI-H CRC, and critically assesses emerging strategies for MSS disease. We propose that future progress will likely depend on mechanism-based, biomarker-driven approaches that match specific immune evasion patterns with rationally designed interventions, with the goal of extending immunotherapy benefits to broader CRC populations. This narrative review synthesizes peer-reviewed literature from PubMed and clinical trial registries (2015-2025), prioritizing Phase II/III trials and mechanistic studies.
This study aimed to construct a risk prediction model based on radiomics, circulating tumor cells (CTCs), and dual-center clinical data to predict the invasiveness of lung adenocarcinoma, specifically for discriminating between minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IAC). The clinical value of this model in the precise diagnosis of early-stage lung adenocarcinoma was investigated to provide a reference for formulating reasonable treatment plans. Clinical data, imaging data, CTCs, and pathological information from 202 patients with lung adenocarcinoma were retrospectively collected and analyzed from two medical centers between May 2022 and July 2023. The 146 cases from medical center 1 were randomly divided into a development set and an internal test set at a 3:2 ratio. The 56 cases from medical center 2 served as an external validation set. Machine learning was employed to analyze preoperative CTC counts and CT radiomic features. A feature selection method based on LASSO regression (with λ determined by the minimum criterion) was used to screen out 12 radiomic features. These features were subsequently incorporated into logistic regression to construct three prediction models: (1) a radiomics model based on radiomic features; (2) a CTCs-clinical data model based on the total development set; and (3) a composite clinical data-radiomics-CTCs model integrating the former two. The optimal model was selected to construct a nomogram. Its goodness-of-fit was assessed using a calibration curve (Hosmer-Lemeshow goodness-of-fit test), and its predictive performance was validated in the external validation set. A total of 107 radiomic features were extracted and categorized into 7 groups: 18 (16.8%) first-order features, 24 (22.4%) gray-level co-occurrence matrix (GLCM) features, 14 (13.1%) gray-level dependence matrix (GLDM) features, 16 (15.0%) each for gray-level run length matrix (GLRLM) and gray-level size zone matrix (GLSZM) features, 5 (4.7%) neighboring gray-tone difference matrix (NGTDM) features, and the remaining (13.1%) were shape-based features. In the total development set, significant differences were observed in clinical-imaging semantic features including CEA, CK19, CTC count, and lesion diameter, which were used to construct the clinical model. The area under the curve (AUC) for the radiomics model was 0.896 95% CI:0.832-0.960. The CTCs-clinical model demonstrated superior performance AUC:0.960, 95% CI:0.926-0.994. The composite clinical-radiomics-CTCs model showed the highest predictive accuracy AUC:0.980, 95% CI:0.960-1.000. According to decision curve analysis and the Akaike information criterion, the composite clinical-radiomics-CTCs model outperformed any single clinical or radiomic feature in terms of clinical predictive capability. For assessing the invasiveness of early-stage lung adenocarcinoma, the radiomics approach can effectively discriminate between MIA and IAC. However, compared to single-modality methods, the composite clinical-radiomics-CTCs model offers a novel auxiliary diagnostic method for evaluating the risk of invasiveness in early-stage lung cancer.
Cancers complicated by cardiovascular diseases (CVDs) are increasingly becoming major limiting factors affecting patients' long-term quality of life and clinical outcomes. Systematic identification of therapeutic targets and their clinical development status is crucial for optimizing treatment strategies. Therefore, this study aimed to establish a target-based analytical framework to systematically map the distribution, developmental stage, maturity, and mechanistic characteristics of clinical trials investigating tumors co-occurring with CVD, thereby identifying potential therapeutic targets. We analyzed clinical trial data on treatments for cancers complicated by CVDs. A total of 58 clinical trials were included and examined across multiple dimensions, including target distribution, development stage, and disease relevance. Forty-five therapeutic targets were identified, with coagulation Factor X, thrombin, and serpin family C member 1 (SERPINC1) emerging as high-frequency core targets. Most studies focused on coagulation, inflammation, and endothelial pathways. Significant variations were observed in completion status and research phase across different targets, with some demonstrating dual therapeutic and cardiovascular regulatory potentials. Coagulation and endothelium-related targets emerged as key links between cancer progression and cardiovascular complications. SERPINC1 and 3-hydroxy-3-methylglutaryl-CoA reductase showed potential for synergistic therapy. This study provides a comprehensive overview of targeted therapies for tumors with concomitant CVD, revealing key pathways and under-explored mechanisms. It offers data-driven insights and directional guidance for precision treatment design.
Hypoalbuminemia is commonly seen in cancer patients. Albumin is essential in drug binding and distribution, particularly in medications with a binding affinity of ≥95% such as tyrosine kinase inhibitors (TKIs). However, hypoalbuminemia can cause an increase in free drug concentration of highly protein-bound drugs, which can enhance drug exposure and cause adverse events. Hypoalbuminemia can significantly affect pharmacokinetics, increasing free drug concentrations and unbound drug in plasma as a consequence of low albumin levels. These alterations in pharmacokinetics can affect patients' tolerability to medications. The study aims to elucidate the impact of albumin levels on medication tolerability and the incidence of adverse events in adult patients with solid tumors. A retrospective cohort study was conducted of all adult patients with solid tumors receiving tyrosine kinase inhibitors (TKIs) with ≥95% protein binding at the Ministry of National Guards Health Affairs-affiliated hospitals, Riyadh, Saudi Arabia. Electronic medical records were reviewed to identify eligible patients initiated on TKIs between January 1, 2016 and December 31, 2022. The main outcomes of this study were survival proportions, grading adverse events, and treatment failure rates in relation to albumin levels. The study included 127 patients out of 450 patients receiving 19 oral TKIs and were divided into two groups (Group A: 51.2% with hypoalbuminemia, and Group B: 48.8% without hypoalbuminemia). Results reveal a significant correlation between hypoalbuminemia and decreased survival proportions by 22% (p-value= 0.04). Additionally, the study identifies a pattern in severity of adverse events, with grade 1 being the most common. Treatment failure is observed more frequently in patients with hypoalbuminemia compared to those with normal albumin levels. This study conducted among a Saudi population demonstrates the critical role of serum albumin levels in predicting TKIs tolerability and treatment success in patients with solid tumors. Assessing and addressing nutritional status and serum albumin before and during TKI treatment may help clinicians identify high‑risk patients and optimize supportive care. Larger prospective studies in diverse populations are needed to validate these findings.
Osimertinib is one of the standard first-line treatments for advanced epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC). Approximately 25% of patients acquire MET amplification upon disease progression on osimertinib and may respond to combined EGFR-MET inhibition (e.g, osimertinib plus savolitinib). However, whether secondary targetable alterations emerge after dual EGFR/MET inhibition, and whether existing targeted agents retain therapeutic relevance in this setting, remain insufficiently characterized. We report a 59-year-old female non-smoker with stage IV EGFR Leu858Arg-mutated lung adenocarcinoma who sequentially received first-line osimertinib (~9 months), second-line osimertinib plus savolitinib for MET amplification (~20 months), third-line platinum-based chemotherapy with local ablative therapy for oligo-progression, and fourth-line docetaxel. Comprehensive genomic profiling (CGP) of an archival cervical lymph node specimen (resected June 2019) subsequently identified an acquired BRAF-AGK fusion alongside the original EGFR Leu858Arg mutation; MET amplification was no longer detected in this specimen. Fifth-line gefitinib plus trametinib (initiated July 2020) was administered for approximately 19 months. Serial thoracic computed tomography, reassessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, showed a best overall response of stable disease, with the dominant target thoracic lesion decreasing from 16.8 mm at baseline to a nadir of 13.8 mm (17.9% maximum reduction). The course was complicated by central nervous system (CNS) progression managed with brain tumor resection and whole-brain radiotherapy, by transient thoracic re-progression during a 48-day treatment interruption that resolved on retreatment, and by trametinib dose reductions for grade 2 toxicities. This case illustrates that an acquired BRAF fusion may emerge as a potentially targetable bypass alteration in EGFR-mutated MET-amplified NSCLC after progression on combined EGFR-MET inhibition and that the combination of a first-generation EGFR-TKI and a MEK inhibitor can be associated with prolonged systemic disease control. The findings are hypothesis-generating and support the value of CGP at sequential progression points to guide mechanism-based therapy in oncogene-driven NSCLC.
While early gastric cancer (EGC) is generally associated with a favorable prognosis, its clinical outcomes are notably heterogeneous. Unlike advanced gastric cancer requiring uniform intensive treatment, EGC lacks robust biomarkers to identify high-risk patients for personalized therapy. Although both N7-methylguanosine (m7G) modification and long non-coding RNAs (lncRNAs) are involved in tumorigenesis, the prognostic value of m7G-related lncRNAs in EGC remains poorly defined. Based on TCGA-EGC data, we identified m7G-related lncRNAs with prognostic significance and constructed a prognostic model for m7G-related lncRNAs using univariate Cox and LASSO. The expression of the model genes was further validated by qRT-PCR. A series of statistical and bioinformatic analyses, including survival analysis, ROC curves, multivariate Cox regression, GSEA, immune infiltration, tumor mutation burden (TMB), and drug sensitivity assays, were performed to evaluate the prognostic performance and underlying biological characteristics of the signature. A six-m7G-related-lncRNA risk model effectively stratified EGC patients into high- and low-risk groups with significantly distinct overall survival. The risk score was confirmed as an independent prognostic factor by univariate and multivariate Cox analysis. Pathway differences between risk groups were primarily enriched in tumor microenvironment regulation terms. Notably, the high-risk group exhibited an immunosuppressive tumor microenvironment correlated with immune escape. TMB analysis showed a negative correlation between the risk score and TMB, with the high-risk and low-TMB subgroup exhibiting the poorest prognosis. In silico drug sensitivity analysis further suggested that high-risk patients may develop poorer sensitivity to five clinical drugs, including Cisplatin, Oxaliplatin, and Vinorelbine. The six-m7G-related-lncRNA signature represents a promising prognostic tool for EGC that may facilitate personalized risk stratification and guide clinical decision-making regarding adjuvant or immunotherapeutic strategies.
Prostate cancer (PCa) is a common urogenital malignancy in elderly males. The typical clinical presentation of advanced PCa includes symptoms of the lower urinary tract. The most common sites of metastasis are the bone and regional lymph nodes. However, PCa with cervical lymphadenopathy as the initial symptom is extremely rare, and one of its variants, foamy gland adenocarcinoma, is even rarer. We present a case of a patient with foamy gland adenocarcinoma of the prostate having enlarged lymph nodes in the neck as the initial symptom. An 81-year-old male was admitted to the hospital with a chief complaint of an enlarged left cervical lymph node without any urological history. Cervical ultrasound showed multiple lymphadenopathies in the left supraclavicular region. The patient underwent a lymph node biopsy, and the pathology results revealed metastatic foamy gland adenocarcinoma of the prostate. Distant lymph node metastasis in PCa is a rare form of metastasis. The initial presentation and tests led to the diagnosis of foamy gland adenocarcinoma of the prostate with cervical lymph node metastasis. Following the diagnosis, the patient received conservative management with androgen deprivation therapy (bicalutamide and goserelin) and zoledronic acid. Unfortunately, he passed away 9 months later due to a COVID-19 infection. We present this rare variant of PCa metastasis to attract the attention of clinicians and pathologists.
Pancreatic cancer (PC) is one of the most aggressive gastrointestinal malignancies, characterized by a dismal 5-year survival rate. This poor prognosis is primarily attributed to delayed early detection, rapid disease progression, surgical complexities, and the limited efficacy of conventional oncological therapies. Extracellular vesicles (EVs) are nanoscale, cell-secreted vesicles that transport bioactive cargoes, including nucleic acids, proteins, and lipids. Upon release into the extracellular space, EVs facilitate short and long-distance intercellular communication and molecular transport via multiple pathways. In this review, we elucidate the multifaceted roles of EVs within the highly malignant PC microenvironment, specifically focusing on their mediation of intricate crosstalk between tumor and stromal cells. Furthermore, we summarize potential EV-based biomarkers for PC diagnosis and the recent advances in leveraging EVs as therapeutic platforms across radiotherapy, gene therapy, and immunotherapy. Ultimately, this review aims to provide novel insights into the clinical management of PC to improve patient outcomes and quality of life.
This article employs a narrative review approach to systematically elucidate the pathophysiological mechanisms of Cushing Syndrome (CS), with a particular focus on exploring the theoretical foundations, clinical applications, and future directions of Traditional Chinese Medicine (TCM) in its treatment. CS is an endocrine disorder caused by chronic excessive cortisol secretion, with dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis at its core. The article first outlines the epidemiological characteristics, pathophysiological mechanisms (including abnormalities in the cAMP/PKA signaling pathway and autocrine/paracrine dysregulation), and genetic basis (such as mutations in ARMC5, PRKACA, and other genes) of CS. Regarding diagnosis, it reviews the application of clinical symptom evaluation, biochemical tests (eg, dexamethasone suppression tests), and imaging techniques (eg, MRI, CT). The core of this review lies in its systematic evaluation of TCM's comprehensive strategies in treating CS. It provides a detailed analysis of the clinical application of TCM, including herbal formulations (eg, Buzhong Yiqi Decoction, Xiaoyao Powder variations), non-pharmacological therapies (eg, acupuncture, tuina), and integrated approaches, while summarizing potential evidence of their efficacy in alleviating symptoms, modulating immunity, and improving quality of life. Concurrently, it points out that the field currently lacks high-quality clinical research support, and that the mechanisms of action and standardized treatment protocols require further investigation. Finally, the article looks forward to the prospects of integrating TCM with modern medicine in treating CS, as well as future directions in basic research, clinical trials, and international collaboration. The aim is to provide a theoretical basis and practical reference for the treatment of CS with TCM.