OncoTargets and therapy最新文献

Immunotherapy is one of the research hotspots in colorectal cancer field in recent years. The colorectal cancer patients with mismatch repair-deficient (dMMR) or high microsatellite instability (MSI-H) are the primary beneficiaries of immunotherapy. However, the vast majority of colorectal cancers are mismatch repair proficient (pMMR) or microsatellite stability (MSS), and their immune microenvironment is characterized by "cold tumors" that are generally insensitive to single immunotherapy based on immune checkpoint inhibitors (ICIs). Studies have shown that some pMMR/MSS colorectal cancer patients regulate the immune microenvironment by combining other treatments, such as multi-target tyrosine kinase inhibitors, anti-vascular endothelial growth factor (VEGF) monoclonal antibodies, chemotherapy, radiotherapy, anti-epithelial growth factor receptor (EGFR) monoclonal antibodies, and mitogen-activated protein kinase (MAPK) signaling pathway inhibitors and oncolytic viruses, etc. to transform "cold tumor" into "hot tumor", thereby improving the response to immunotherapy. In addition, screening for potential prognostic biomarkers can also enrich the population benefiting from immunotherapy for microsatellite stable colorectal cancer. Therefore, in pMMR or MSS metastatic colorectal cancer (mCRC), the optimization of immunotherapy regimens and the search for effective efficacy prediction biomarkers are currently important research directions. In this paper, we review the progress of efficacy of immunotherapy (mainly ICIs) in pMMR /MSS mCRC, challenges and potential markers, in order to provide research ideas for the development of immunotherapy for mCRC.

Background: This study investigates the prognostic value of M0 macrophage-related genes (M0MRGs) in esophageal cancer (ESCA) and identifies novel targets for immunotherapy.

Methods: Differentially expressed genes (DEGs) were screened with ESCA-related expression profile data (GSE5364 and GSE17351) from the GEO database, followed by GO and KEGG pathway enrichment analyses. Then, immune cell infiltration was examined with the CIBERSORT algorithm and multiplex fluorescence-based immunohistochemistry (MP-IHC). ESCA-related gene expression data and relevant clinical information were retrieved from TCGA. M0MRGs were identified with TCGA-ESCA based on Spearman's correlation coefficient. Additionally, LASSO and Cox regression analyses were conducted to further construct an M0MRG-related prognostic model. ATP6V0D2 and MMP12 expression in ESCA was analyzed with tissue microarray. Finally, the half maximal inhibitory concentrations (IC50) of commonly used chemotherapeutics in TCGA-ESCA were calculated with the "oncoPredict" R package.

Conclusion: In summary, ATP6V0D2 and MMP12 were crucial components in a prognostic risk model for ESCA and were associated with poor prognoses, implicating the involvement of elevated M0 macrophages in disease progression and providing potential therapeutic targets and strategies for ESCA.

Introduction: The FGFR3-TACC3 fusion gene exists in a variety of malignant tumors, including bladder cancer. In our ongoing research on the CRISPR-Cas13a gene-editing system, we reported the use of CRISPR-Cas13a gene-editing system to knockout FGFR3-TACC3 and inhibit the proliferation of bladder tumor cells.

Purpose:  This study aimed to use the CRISPR-Cas13a gene-editing system to target the FGFR3-TACC3 fusion gene in bladder cancer cells, which has the potential to be a new and effective treatment for bladder cancer.

Materials and methods: The efficacy of the CRISPR-Cas13a gene-editing system was analysed by qRT-PCR. The inhibitory effects of Cas13a-mediated knockdown of the FGFR3-TACC3 fusion gene on the proliferation of RT4 and RT112 cell lines were assessed utilizing CCK-8, EdU, and organoid formation assays. Subsequently, the comparative tumorigenic capability of RT4 cells with FGFR3-TACC3 knockdown achieved by Cas13a was examined in a nude mouse model.

Results: At the cellular level, the comparative analysis of FGFR3-TACC3 knockdown efficacy between CRISPR-Cas13a and shRNA revealed a more pronounced reduction with the former. This knockdown effectively curtailed cellular proliferation, with CRISPR-Cas13a-mediated knockdown exhibiting a superior inhibitory effect over shRNA-mediated knockdown. In organoid cultures derived from RT4 cells, a similar trend was observed, with Cas13a-mediated knockdown of FGFR3-TACC3 leading to a more substantial suppression of proliferation compared to shRNA-mediated knockdown. In vivo tumor models corroborated these findings, demonstrating a significantly diminished tumor volume in the Cas13a-treated cohort relative to both the control and shRNA-treated groups.

Conclusion: The CRISPR-Cas13a gene-editing system has been demonstrated to significantly suppress tumor proliferation both in vitro and in vivo, thereby presenting itself as a promising candidate for a novel and efficacious therapeutic intervention in bladder cancer treatment.

[This corrects the article DOI: 10.2147/OTT.S474055.].

[This retracts the article DOI: 10.2147/OTT.S242715.].

Background: Alectinib is a second generation of anaplastic lymphoma kinase (ALK) inhibitor that has been approved for the treatment of advanced non-small-cell lung cancer (NSCLC) with ALK rearrangements. Hepatotoxicity is the most common adverse drug reaction. However, there is currently no published report on the pathologic findings of alectinib-induced hyperbilirubinemia.

Case presentation: Here, we report a case of a patient with NSCLC and chronic hepatitis B (CHB) who was treated with alectinib and developed grade 4 hyperbilirubinemia after 3 years on therapy. Alectinib was discontinued, and an artificial liver support system (ALSS) was used to decline blood bilirubin levels. The pathological manifestations from a liver biopsy showed the hepatocytes with scattered focal necrosis, bile stasis, and vesicular steatosis, bile emboli in capillaries, and star-shaped fibers proliferation in the portal area.

Conclusion: This is the first report of alectinib-induced hyperbilirubinemia which was confirmed by liver histopathology and successfully relieved by ALSS treatment and drug discontinuation.

Objective: MiRNAs play a pivotal role in tumorigenesis and development by exerting negative regulation on the expression of target genes. In this study, bioinformatics techniques and online database were employed to investigate the specific miRNA-target gene regulatory network in PTC, which was subsequently validated using human blood samples and compared to existing tumor markers.

Methods: The miRNA (GSE50901) and Gene Expression (GSE113629) chip screening data of human PTC tissues were retrieved from GEO database. A comparative analysis was conducted using the GEO2R to identify differentially expressed miRNAs and target genes of the patients with PTC. Prediction of the miRNA-target gene regulatory network, related signal transduction pathways, biological effects and their relationship to prognosis was performed based on GO, KEGG, qRT-PCR detection of human blood samples, analysis of correlation on the existing pathological tumor markers, and ROC.

Results: Compared to the corresponding normal thyroid tissues, a total of 2116 miRNAs were found to be differentially expressed in PTC patients, including 1968 up-regulated and 148 down-regulated genes. The abnormally expressed genes primarily participated in signal pathways associated with tumorigenesis and abnormal gene transcription. By utilizing data from the GEO database, five miRNAs closely linked to PTC prognosis were identified, which were miR-221-3p, miR-222-3p, miR-182-5p, miR-135a-5p, and miR-34a-5p, with elucidating the target genes. Experimental validation, correlation analysis with tumor markers along with bioinformatics analysis revealed a significant increase in expression levels of miR-182-5p in PTC patients which positively correlated with poor prognosis. These molecules could play crucial roles in both initiation and progression of PTC.

Conclusion: This study identified potential novel blood-based miRNA biomarkers for PTC through bioinformatics analysis combined with the detection of human blood samples, thereby offering new possibilities for significant biomarkers associated with diagnosis and prognosis of PTC.

UBE2C (Ubiquitination-binding enzyme 2C), one of the E2 enzymes encoded in the human genome, is a component of the ubiquitin proteasome system and plays a pivotal role in regulating cell cycle progression. Moreover, UBE2C is highly expressed and may play a pivotal role in both high-incidence and high-mortality malignancies, including lung cancers, breast cancers, and esophageal cancers. UBE2C influences a number of key processes, including cell cycle progression, tumor invasion and metastasis, proliferation, and drug resistance. However, few articles have systematically summarized the role of UBE2C in cancer. The aim of this review is to describe the structure and function of UBE2C, focusing on the current status of UBE2C research in malignant tumors. Furthermore, this review presents the potential of UBE2C as a new therapeutic target and a diagnostic and prognostic biomarker. Finally, future research directions for UBE2C are proposed. It is of great value to explore the mechanism of action of UBE2C in the tumor microenvironment (TME). A comprehensive and coherent comprehension of UBE2C will undoubtedly facilitate its transition from fundamental research to clinical applications.

[This retracts the article DOI: 10.2147/OTT.S226915.].

Purpose: We aimed to determine the safety and feasibility of neoadjuvant immunotherapy combined with sandwich chemoradiotherapy in patients with locally advanced nasopharyngeal carcinoma (NPC).

Patients and methods: This retrospective study involved 37 patients with locally advanced NPC treated with the above regimen. All patients received four cycles of neoadjuvant immunotherapy and chemotherapy at three-week intervals, including the administration of PD-1 inhibitors, namely, sintilimab (a fixed dose of 200 mg on Day 1) or toripalimab (240 mg on Day 1). The chemotherapy program consisted of nab-paclitaxel (260 mg/m2, Day 1) plus nedaplatin (85 mg/m2, Day 1). Concurrent with intensity-modulated radiation therapy (IMRT), the patients received targeted drug therapy with nimotuzumab (200 mg) across six cycles. Finally, 4 cycles of S-1 adjuvant chemotherapy were administered.

Results: In this study, the efficiency of neoadjuvant immunotherapy combined with chemotherapy was 94.6%, the CR rate was 67.6%, and the efficiency 3 months after IMRT was 100%. The 2-year overall survival (OS), locoregional control (LCR), distant metastasis-free survival (DMFS), and progression-free survival (PFS) rates of the whole group were 97.3%, 94.6%, 97.3% and 91.9%, respectively. Neutropenia was the most common hematological toxicity (100%), and the incidence of grade ≥ 3 neutropenia was 40.5%. Grade 3 anemia and thrombocytopenia did not occur. Additionally, no adverse reactions, such as hypothyroidism, immune pneumonia, or myocarditis, occurred in the whole group. However, the incidences of rash, musculoskeletal pain, and hepatotoxicity were high (45.9%, 54.1% and 37.8%, respectively).

Conclusion: The survival benefit of neoadjuvant immunotherapy combined with sandwich chemoradiotherapy is excellent, with tolerable toxicity, in patients with locally advanced NPC. This study provides new insight into the application of immunotherapy in locally advanced NPC.