OncoTargets and therapy最新文献

We present a 57-year-old female diagnosed with stage cT3N1M1a (IVA) EGFR L858R-mutant lung adenocarcinoma (PD-L1 TPS 60%). The patient attained sustained disease control with a partial response lasting 22 months on first-line gefitinib. Following progression with persistent EGFR L858R mutation, second-line platinum-pemetrexed-bevacizumab chemotherapy achieved stable disease (SD) in the primary lesion and shrinkage of pleural nodules. Subsequent neoadjuvant therapy with albumin-bound paclitaxel, carboplatin, bevacizumab, and sintilimab induced marked tumor regression, permitting curative-intent R0 resection. Histopathological analysis confirmed ypT0N0, indicating a pathological complete response (pCR). The patient remained recurrence-free 25 months post-surgery. This case illustrates the potential of immunotherapy-based neoadjuvant regimens to convert unresectable PD-L1-high EGFR-mutant lung adenocarcinoma into operable disease and achieve durable pCR.

[This retracts the article DOI: 10.2147/OTT.S272596.].

Background: Ovarian cancer is a leading cause of gynecologic cancer-related deaths, with cisplatin (DDP) resistance posing a significant challenge to effective treatment. Understanding the molecular mechanisms underlying DDP resistance is crucial for developing new therapeutic strategies.This study aimed to explore the molecular mechanisms of DDP resistance in ovarian cancer, focusing on identifying key genes involved in this process.

Methods: Differential gene expression analysis was conducted using three GEO datasets to identify genes associated with DDP resistance in ovarian cancer cells. Functional enrichment analysis was performed to elucidate the biological pathways involved. ANXA4 was identified as a key gene, and its role was further investigated through in vitro experiments, including gene silencing and overexpression assays, to assess its impact on cell viability, apoptosis, and epithelial-mesenchymal transition (EMT) markers.

Results: A total of 33 common differentially expressed genes (DEGs) were identified, with ANXA4 significantly upregulated in DDP-resistant ovarian cancer cells. Functional analysis revealed that these DEGs, including ANXA4, were involved in pathways related to cell survival, proliferation, and apoptosis. In vitro experiments showed that silencing ANXA4 decreased cell viability, increased apoptosis, and reversed EMT markers in DDP-resistant cells. Conversely, ANXA4 overexpression enhanced resistance to DDP, as evidenced by increased cell viability, reduced apoptosis, and upregulation of EMT markers.

Conclusion: ANXA4 plays a critical role in promoting DDP resistance in ovarian cancer by enhancing cell survival, inhibiting apoptosis, and maintaining EMT characteristics. Targeting ANXA4 may offer a novel therapeutic strategy to overcome chemoresistance and improve treatment outcomes in patients with ovarian cancer. Future studies should validate these findings in vivo and explore the precise molecular mechanisms by which ANXA4 modulates DDP resistance.

Purpose: Sensitivity to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) varies among individuals harboring exon 19 deletions (19del) at different amino acid positions and EGFR 19del or deletion-insertions (19delins), and the role of chemotherapy in this context remains unknown. Therefore, we investigated how chemotherapy and the EGFR 19del subtype affect the clinical outcomes of patients with advanced non-small cell lung cancer (NSCLC) treated with first-generation TKIs.

Patients and methods: Eighty patients at one hospital who harbored an EGFR 19del mutation were retrospectively included. Survival analyses were performed by comparing first-line treatments, EGFR 19del variants, and the coding positions at which the deletions began.

Results: Among the 80 patients, 37 and 43 received first-generation TKIs and TKIs and chemotherapy, respectively. Progression-free survival (PFS) and overall survival (OS) were comparable between the two groups. The results were the same for patients with the EGFR p.E746 mutation (n = 56) and those with the p.L747 mutation (n = 23). However, in the subgroup of patients treated with TKIs, the results favored patients with EGFR p.E746 mutations over those with p.L747 mutations, as the median PFS differed by 4 months. In the EGFR p.L747 subgroup, PFS and OS were significantly longer in patients treated with chemotherapy and TKIs than in those treated with TKIs alone. Both EGFR p.L747 and treatment with TKIs were significant risk factors for poor PFS. Eastern Cooperative Oncology Group performance status was the only significant independent risk factor for poor OS. Compared with TKIs alone, combination therapy was associated with more grade III or IV toxicity effects.

Conclusion: Additional chemotherapy did not benefit patients with p.E746 mutations but did significantly improve the PFS and OS of those with p.L747 mutations. Thus, chemotherapy + first-generation TKI combination therapy for patients with advanced NSCLC should be carefully selected.

Purpose: Monocytes and macrophages are recognized as predominant immune populations in human glioblastoma, where they play vital roles in tumor progression. Despite their established significance, the heterogeneity of these cells-particularly within the monocyte compartment-remains incompletely characterized.

Methods: We comprehensively used scRNA-seq, spatial transcriptome sequencing combined with immunofluorescence and T cell co-culture assays to illuminate the heterogeneity and function of monocyte in glioblastoma.

Results: In this study, from the perspective of ligand-receptor networks, we have identified and characterized three distinct glioblastoma subtypes. Single-cell RNA-seq analysis further revealed that the C3 subtype with bad prognosis exhibited a higher proportion of S100A9^high monocytes. Spatial transcriptomics combined with immunofluorescence assays demonstrated that these S100A9^high monocytes were spatially adjacent to M2 macrophages, exhausted CD8+ T cells, and endothelial cells. In vitro T cell co-culture assays revealed S100A9^high monocyte produced elevated levels of the immunosuppressive cytokine IL-10, reactive oxygen species (ROS) and inducible nitric oxide synthase (iNOS), all of which might impair T cell function and immune response. Notably, elevated abundance of S100A9^high monocyte correlated with poor patient prognosis.

Conclusion: In summary, our results deciphered the heterogeneity of monocytes in glioblastoma and identified a novel poor prognosis-associated monocyte subset, S100A9^high monocytes, which foster an immunosuppressive, pro-tumorigenic microenvironment.

[This retracts the article DOI: 10.2147/OTT.S280717.].

Objective: This study aimed to evaluate the efficacy and safety of niraparib as a maintenance treatment for newly diagnosed advanced ovarian cancer in a real-world setting.

Methods: This retrospective observational study included patients with histologically confirmed epithelial ovarian cancer, primary peritoneal or fallopian tube cancer who received niraparib as first-line maintenance therapy at Tianjin Cancer Hospital between January 2021 and January 2023. Clinicopathological characteristics and treatment outcomes were extracted from medical records. The efficacy of niraparib was evaluated by progression-free survival (PFS), and safety was assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

Results: A total of 102 patients were enrolled in this study. After a median follow-up of 21.4 months (IQR 20.4-22.5 months), the median PFS was 25.7 months in the overall population, not reached in the BRCA mutation group, and 23.0 months in the wild-type group. A total of fifty patients with a known status of homologous recombination deficiency (HRD) were observed. The median PFS was not reached and 23.0 months in the homologous recombination deficiency and proficient groups, respectively. In the BRCA wild-type group, patients who received more than six cycles of platinum-based chemotherapy had a better prognosis. Furthermore, 20.6% of patients experienced grade 3 or higher treatment-emergent adverse events, while 39.2% experienced treatment interruption, 37.3% underwent dose reduction, and 6.9% discontinued treatment. No new safety signals were observed.

Conclusion: In the real-world setting, the use of niraparib as a maintenance treatment for newly diagnosed advanced ovarian cancer has been shown to be effective and well tolerated, which is consistent with the results of previous randomized Phase III trials.

Laryngeal minor salivary gland carcinoma is a rare malignancy, accounting for less than 1% of laryngeal cancers. We present a case of a 43-year-old male with a history of surgically resected laryngeal ductal carcinoma who developed liver metastases. Initial pathology from the liver lesion was inconclusive, leading to a misdiagnosis of intrahepatic cholangiocarcinoma. After progression on first-line chemotherapy and immunotherapy, the diagnosis was revised to metastatic laryngeal minor salivary gland carcinoma, supported by positive EGFR expression. Second-line treatment with the anti-EGFR agent cetuximab, combined with immunotherapy and chemotherapy (sindilizumab, albumin-bound paclitaxel, and S-1), resulted in a sustained partial response. This case highlights the diagnostic challenges of this rare tumor and suggests the potential efficacy of anti-EGFR therapy in EGFR-expressing metastatic laryngeal salivary gland carcinoma. Given the rarity and aggressive nature of primary laryngeal salivary duct carcinoma, it remains a significant challenge for both diagnosis and treatment. The current case underscores the difficulty in identifying the primary tumor site, especially when metastasis occurs. Additionally, the effectiveness of anti-EGFR therapy in EGFR-expressing tumors offers a promising treatment avenue. Further research is essential to establish standardized treatment protocols, identify predictive biomarkers, and optimize combination strategies for this uncommon malignancy.

Patient-derived organoids (PDOs) are emerging as a potential preclinical tool in assessing cancer patients' responses to various therapies. Here, we first described a case of invasive ductal breast carcinoma with lung and liver metastases who obtained efficient response to the sensitive drugs identified by PDOs. A 54-year-old woman came to hospital with the chief complaint of an unpainful mass in the right breast. In combination with relevant examinations, she was diagnosed with cT3N1M0 breast cancer with HER2 amplification, but developed lung and liver metastases after use of multiple therapies. After treatment with erebulin, carboplatin and inetetamab sensitive revealed by the organoid drug sensitivity testing, partial response in lung metastasis and stable disease in liver metastasis were achieved. This typical case suggests that for the individual patients with advanced refractory breast cancer, especially those exhausting the standard treatment options, the PDOs may serve as an effective model for assessing individual drug sensitivity to optimize treatment decisions and improve treatment response.

Purpose: This study aimed to evaluate the clinical utility of a pan-cancer circulating tumor DNA (ctDNA) next-generation sequencing (NGS) panel for predicting treatment response and progression-free survival (PFS) in patients with advanced solid tumors.

Patients and methods: A total of 41 patients with advanced solid tumors, including gastric cancer (n=13), non-small cell lung cancer (n=10), head and neck cancer (n=9), esophageal cancer (n=7), breast cancer (n=1), and colon cancer (n=1), were prospectively enrolled and included in the analysis. ctDNA was analyzed at three time points: pretreatment (41 patients), post-treatment evaluation (37 patients), and follow-up (18 patients).

Results: Among 41 patients analyzed at pretreatment, 35 (85.4%) exhibited tier 1 or 2 somatic variants in ctDNA, with TP53 being the most frequently mutated gene. At the post-treatment evaluation, ctDNA was assessed in 37 patients (3 with rapid deterioration and 1 lost to follow-up were not evaluable). Newly emerging variants after treatment were strongly associated with poor clinical outcomes. Consistent with the Kaplan-Meier analysis, Cox proportional hazards regression confirmed that post-treatment ctDNA positivity was significantly associated with inferior PFS (HR 10.5, 95% CI 1.4-80.0, P=0.024). At follow-up, 18 patients were evaluable, while the others were not due to follow-up loss, rapid deterioration, or study termination. ctDNA positivity at post-treatment evaluation was significantly associated with shorter PFS (median PFS, 5.0 months [95% CI: 2.0-12.0] vs not reached; HR, 4.87; 95% CI: 1.69-14.09; P = 0.0035).

Conclusion: Longitudinal monitoring of ctDNA using a pan-cancer NGS panel provides meaningful prognostic information in patients with advanced cancers. Post-treatment ctDNA dynamics may better reflect disease progression than baseline ctDNA status alone, highlighting the need for further validation in larger cohorts, particularly in gastric, lung, head and neck, and esophageal cancers.