Clinical Medicine Insights-Oncology最新文献

{"title":"Combination of High-Dose Parenteral Ascorbate (Vitamin C) and Alpha-Lipoic Acid Failed to Enhance Tumor-Inhibitory Effect But Increased Toxicity in Preclinical Cancer Models.","authors":"Ping Chen, Davis Lamson, Paul Anderson, Jeanne Drisko, Qi Chen","doi":"10.1177/11795549241283421","DOIUrl":"10.1177/11795549241283421","url":null,"abstract":"<p><strong>Background: </strong>Intravenous vitamin C (IVC, ascorbate [Asc]) and alpha-lipoic acid (ALA) are frequently coadministered in integrative oncology clinics, with limited understanding of combination effects or drug-drug interactions. As high-dose IVC has anticancer activity through peroxide (H₂O₂), it is hypothesized that IV ALA, a thiol antioxidant, might have untoward effects when combined with IVC.</p><p><strong>Methods: </strong>In vitro combination index (CI) was investigated in 6 types of human cancer cells, using clinically relevant concentrations of Asc (0.625-20 mM) and ALA (0.25, 0.5, and 1 mM) evaluated by nonconstant ratio metrics. Cellular H₂O₂ was measured using HeLa cells expressing a fluorescent probe HyPer. Mouse xenografts of the metastatic breast cancer MDA-MB-231 were treated with intraperitoneal injections of ALA (10, 20, and 50 mg/kg) and Asc (0.2, 0.5, and 4 g/kg) at various dose levels.</p><p><strong>Results: </strong>Cancer cell lines were sensitive to Asc treatment but not to ALA. There is no evidence ALA becomes a prooxidant at higher doses. The CIs showed a mixture of synergistic and antagonistic effects with different ALA and Asc combination ratios, with a \"U\" shape response to Asc concentrations. The ALA concentrations did not influence the CIs or cellular H₂O₂ formation. Adding ALA to Asc dampened the increase of H₂O₂. Toxicity was observed in mice receiving prolonged treatment of ALA at all doses. The Asc at all doses was nontoxic. The combination of ALA and Asc increased toxicity. The ALA at all doses did not inhibit tumor growth. The Asc at 4 g/kg inhibited tumor growth. Adding ALA 50 mg/kg to Asc 4 g/kg did not enhance the effect, but lower doses of ALA (10 or 20 mg/kg) dampened the inhibitory effect of Asc.</p><p><strong>Conclusions: </strong>These data do not support the concurrent or relative concurrent use of high-dose intravenous ALA with prooxidative high-dose IVC in clinical oncology care with potentially increased toxicity.</p>","PeriodicalId":48591,"journal":{"name":"Clinical Medicine Insights-Oncology","volume":"18 ","pages":"11795549241283421"},"PeriodicalIF":1.9,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528587/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic Reprogramming of Cancer-Associated Fibroblast in the Tumor Microenvironment: From Basics to Clinic.","authors":"Lujia Zhou, Wenjie Zhang, Xiaoxue Hu, Daorong Wang, Dong Tang","doi":"10.1177/11795549241287058","DOIUrl":"https://doi.org/10.1177/11795549241287058","url":null,"abstract":"<p><p>Metabolic reprogramming occurs when tumor cells replenish themselves with nutrients required for growth to meet their metabolic needs. Cancer-associated fibroblasts (CAFs) are activated fibroblasts involved in building the c (TME) to promote tumor progression and metastasis. Metabolic reprogramming of CAFs can interact with cancer cells to generate metabolic crosstalk. Furthermore, CAF metabolic reprogramming has great potential as a new field of tumor treatment. This review summarizes the role of CAFs in TME and the mechanisms by which metabolic reprogramming of CAFs causes cancer progression and metastasis, demonstrating the great potential of CAF metabolic reprogramming in cancer chemotherapy and immunotherapy treatment. Furthermore, we provide an outlook for future CAF metabolic reprogramming for cancer treatment.</p>","PeriodicalId":48591,"journal":{"name":"Clinical Medicine Insights-Oncology","volume":"18 ","pages":"11795549241287058"},"PeriodicalIF":1.9,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11500237/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142510836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential Role of <i>AKR1B1</i> Gene Methylation in Diagnosis of Patients With Breast Cancer.","authors":"Mohamed El-Far, Mohamed A Abdelrazek, Basma M Foda, Amr Abouzid, Menha Swellam","doi":"10.1177/11795549241290796","DOIUrl":"https://doi.org/10.1177/11795549241290796","url":null,"abstract":"<p><strong>Background: </strong>In addition to the great challenge of early diagnosis and prognosis in breast cancer (BC), the role of gene promoters in BC remains largely unexplored. This study aimed to evaluate aldo-keto reductase family 1 member B1 (<i>AKR1B1</i>) methylation as noninvasive biomarker for early BC diagnosis.</p><p><strong>Methods: </strong>A total of 200 (120 with BC, 40 with benign breast diseases, 40 healthy) Egyptian women were enrolled. <i>AKR1B1</i> methylation level was determined using EpiTect Methyl II QPCR assay quantitative polymerase chain reaction.</p><p><strong>Results: </strong>Findings revealed that hypermethylation <i>AKR1B1</i> was reported to be associated (<i>P</i> < .0001) with BC cases (93.2 [75.4-98.6]) compared with benign (23.9 [22.6-48.3]) or healthy (15.5 [10.6-16]) controls. It had a great diagnostic power (area under the curve [AUC] = 0.909) that was superior to cancer antigen (CA) 15-3 (AUC = 0.681) and carcinoembryonic antigen (CEA) (AUC = 0.539). Interestingly, <i>AKR1B1</i> hypermethylation was reported to be significant in identifying BC early stages (AUC = 0.899) and grades (AUC = 0.903). Independent to hormonal status and HER2neu expression, <i>AKR1B1</i> hypermethylation was related to some tumor severity features, including advanced stages, high histological grades, and lymph node invasion. Also, <i>AKR1B1</i> high degrees of methylation were significantly correlated with the increase in CEA (<i>r</i> = .195; <i>P</i> = .027), CA-15.3 (<i>r</i> = .351; <i>P</i> = .0001) and tumor stages (<i>r</i> = .274; <i>P</i> = .014), grades (<i>r</i> = .253; <i>P</i> = .024), and lymph node invasion (<i>r</i> = .275; <i>P</i> = .014).</p><p><strong>Conclusions: </strong>This study revealed that aberrant <i>AKR1B1</i> methylation could facilitate early BC detection from benign br0east disorders. Hypermethylated <i>AKR1B1</i> was related to BC aggressiveness suggesting its potential role as diagnostic and prognostic BC biomarker.</p>","PeriodicalId":48591,"journal":{"name":"Clinical Medicine Insights-Oncology","volume":"18 ","pages":"11795549241290796"},"PeriodicalIF":1.9,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11497498/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142510837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early-Stage Renal Cell Carcinoma Locoregional Therapies: Current Approaches and Future Directions.","authors":"Umang Khandpur, Bereket Haile, Mina S Makary","doi":"10.1177/11795549241285390","DOIUrl":"10.1177/11795549241285390","url":null,"abstract":"<p><p>Renal cell carcinoma (RCC) is the most common primary renal malignancy. Prevalence of RCC in developed countries has slowly increased. Although partial or total nephrectomy has been the first-line treatment for early-stage RCC, improved or similar safety and treatment outcomes with locoregional therapies have challenged this paradigm. In this review, we explore locoregional techniques for early-stage RCC, including radiofrequency ablation, cryoablation, and microwave ablation with a focus on procedural technique, patient selection, and safety/treatment outcomes. Furthermore, we discuss future advances and novel techniques, including radiomics, combination therapy, high-intensity focused ultrasound, and catheter-directed techniques.</p>","PeriodicalId":48591,"journal":{"name":"Clinical Medicine Insights-Oncology","volume":"18 ","pages":"11795549241285390"},"PeriodicalIF":1.9,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11492234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Utility of Circulating Tumor DNA Assay in Identifying Mutations and Guiding Matched Targeted Therapy in Lung Cancers.","authors":"Kun Li, Nana Zhang, Bing Xu, Zichen Liu, Dan Zhao, Yujie Dong, Jing Mu, Haifeng Lin, Guangyu Shan, Sihang Gao, Bo Yu, Xiaoxi Pan, Yanrong Wang, Dongxing Zhang, Nanying Che, Xiaoyong Ji","doi":"10.1177/11795549241285238","DOIUrl":"10.1177/11795549241285238","url":null,"abstract":"<p><strong>Background: </strong>Tumor genomic profiling has a significant impact on the selection of targeted therapy. Circulating tumor DNA (ctDNA) has emerged as a noninvasive, and reproducible assay compared with tissue biopsy. We aimed to evaluate its utility in identifying mutations and guiding targeted therapy for lung cancer.</p><p><strong>Methods: </strong>A total of 173 lung cancer patients underwent next-generation sequencing (NGS) using a targeted enrichment panel covering 20 lung cancer-related genes. The performance of the ctDNA NGS assay in identifying genetic mutations or alterations was compared with tissue biopsy and droplet digital PCR (ddPCR). The treatment response to epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapies based on the ctDNA assay results was also assessed.</p><p><strong>Results: </strong>The ctDNA was detected in 61.85% of patients. Tissue mutations were detected in paired ctDNA in 38.57% of cases, while ctDNA mutations were detected in paired tissues in 89.1% of cases. The ctDNA increased the number of advanced non-small cell lung cancer (NSCLC) patients who received NCCN-recommended genetic testing by 12%. The concordance between ddPCR and ctDNA was relatively high reaching 99.43%. <i>EGFR</i> T790M/C797S c.G2390C and <i>EGFR</i> T790M/C797S c.T2389A were detected in tissue and ctDNA, respectively, in patient 01015. Moreover, ctDNA assay identified the <i>EGFR</i> T790M mutation, which was missed by tissue biopsy in patient 01149, who developed drug resistance after 1 year of EGFR-TKI therapy. Of the 17 patients who received EGFR-TKI targeted therapies based on the ctDNA NGS results, 12 patients achieved a partial response and two patients had stable disease.</p><p><strong>Conclusions: </strong>The results demonstrated that the ctDNA assay could partially overcome tumor heterogeneity in detecting mutations and provide complementary information on tumor genomic profiles. Moreover, the presence of <i>EGFR</i> mutations in ctDNA could offer valuable guidance for selecting appropriate EGFR-TKI treatment for advanced lung cancer patients. However, it is important to note that the ctDNA NGS assay has certain limitations in fully identifying all genomic alterations present in the tumor.</p>","PeriodicalId":48591,"journal":{"name":"Clinical Medicine Insights-Oncology","volume":"18 ","pages":"11795549241285238"},"PeriodicalIF":1.9,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11489900/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dendritic Cells Loaded With Heat Shock Inactivated Glioma Stem Cells Enhance Antitumor Response of Mouse Glioma When Combining With CD47 Blockade.","authors":"Qijia Tan, Feng Li, Jun Wang, Yi Liu, Yingqian Cai, Yuxi Zou, Xiaodan Jiang","doi":"10.1177/11795549241285239","DOIUrl":"10.1177/11795549241285239","url":null,"abstract":"<p><strong>Background: </strong>For glioma patients, the long-term advantages of dendritic cells (DCs) immunization remain unknown. It is extremely important to develop new treatment strategies that enhance the immunotherapy effect of DC-based vaccines. DCs exposed to glioma stem cells (GSCs) are considered promising vaccines against glioma.</p><p><strong>Methods: </strong>Glioma stem cells were isolated from mouse glioma GL261 cells (GCs). Both were subjected to severe (47°C) and mild (42°C) heat shock to induce immunogenic cell death (ICD). Membrane mobilization of calreticulin (CRT) and release of heat shock proteins (HSPs) were detected by flow cytometry. Dendritic cells were then exposed to heat-inactivated cells and co-culturing of T cells tested for immunotherapeutic efficacy in vitro. In vivo, we investigated the GSC targeting effect of the GSC-DC vaccine combined with CD47 blockade.</p><p><strong>Results: </strong>Heat shock induced ICD in GCs and GSCs, as indicated by significant release of calreticulin, HSP70, and HSP90. Heat shock condition ICD lysates induce maturation and activation-associated marker expression on monocyte-derived DCs. Accordingly, DCs pulsed with GCs and GSCs inactivated reduced colony formation, sphere formation, migration, and invasion of glioma and GSCs in vitro. Glioma stem cell-DC vaccine in combination with anti-CD47 antibody significantly enhanced survival in mice with glioma, induced production of interferon (IFN)-γ, and enhanced T-cell expansion in vivo. Of note, DCs pulsed with inactivated GSCs were more effective to control tumor growth than DCs pulsed with inactive GCs.</p><p><strong>Conclusions: </strong>Severe heat shock induces ICD in vitro. These data showed that administration of anti-CD47 antibody combined with GSC-DC vaccine may represent an effective immunotherapeutic strategy for cancer patients in clinical.</p>","PeriodicalId":48591,"journal":{"name":"Clinical Medicine Insights-Oncology","volume":"18 ","pages":"11795549241285239"},"PeriodicalIF":1.9,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11487516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of CREBBP and EP300 Associated With Tumor Volume in Patients With Grade-3 Glioma: A Retrospective Analysis.","authors":"Cuiwei Chen, Meiqin Yuan, Liang Xia, Xin Wu, Xingguang Zhong, Huangjie Zhang, Lidan Zhang, Xuan Liu, Zeng Wang, Caixing Sun","doi":"10.1177/11795549241287777","DOIUrl":"10.1177/11795549241287777","url":null,"abstract":"<p><strong>Background: </strong>Reliable predictive data are crucial for making accurate treatment decisions in glioma patients, but it can be challenging to obtain due to limited information in many cases. Numerous research studies have indicated the involvement of cyclic adenosine monophosphate (cAMP)-response element binding protein (CREBBP) and E1A binding protein p300 (EP300) in tumorigenesis and tumor progression across various types.</p><p><strong>Methods: </strong>The messenger RNA (mRNA) expression levels of CREBBP and EP300 were retrospectively analyzed in 17 grade-3 glioma patients. The SYBR Green real-time polymerase chain reaction (RT-PCR) technique was employed for mRNA expression analysis, with the glyceraldehyde-3-phosphate dehydrogenase gene (<i>GAPDH</i>) used as a reference gene for data normalization. In addition, the relationship between CREBBP, EP300 expression and patients' clinical information, imaging features, histologic features, immune factors, and overall survival was assessed through univariate analyses.</p><p><strong>Results: </strong>The analysis of the data unveiled a statistically significant upregulation of CREBBP and EP300 mRNA expression levels in large gliomas as compared with their smaller counterparts (<i>P</i> < .05). Histological examination using hematoxylin and eosin (H&E) staining exhibited marked cellular heterogeneity, with heightened cell density observed specifically within tumors displaying elevated CREBBP expression levels. In contrast, there was a substantial downregulation of complement 3 and complement 4 within larger tumor volumes when compared with smaller ones (<i>P</i> < .05). However, these findings do not serve as clinically relevant prognostic indicators for glioma.</p><p><strong>Conclusions: </strong>It is suggested that higher expression levels of CREBBP and EP300 are positively associated with increased tumor volume. Inhibition of CREBBP and EP300 enhances local immunogenicity, leading to the recruitment of immune cells and release of cytokines for effective tumor eradication, ultimately resulting in the inhibition of tumor growth.</p>","PeriodicalId":48591,"journal":{"name":"Clinical Medicine Insights-Oncology","volume":"18 ","pages":"11795549241287777"},"PeriodicalIF":1.9,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11490948/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined Positive Score and Cisplatin Sensitivity Are Prognostic Factors for Response to Nivolumab Therapy for Recurrent Metastatic Squamous Cell Carcinoma of the Head and Neck.","authors":"Hiroaki Iijima, Akihiro Sakai, Koji Ebisumoto, Go Ogura, Mayu Yamauchi, Takanobu Teramura, Aritomo Yamazaki, Takane Watanabe, Toshihide Inagi, Ryoko Yanagiya, Ai Yamamoto, Hiroshi Ashida, Yoshiyuki Ota, Yurina Sato, Naoya Kobayashi, Daisuke Maki, Naoya Nakamura, Kenji Okami","doi":"10.1177/11795549241290030","DOIUrl":"10.1177/11795549241290030","url":null,"abstract":"<p><strong>Background: </strong>Recurrent or metastatic squamous cell carcinoma of the head and neck (R/MHNSCC) is a challenging malignancy with a poor prognosis and limited treatment options. Nivolumab, an immune checkpoint inhibitor (ICI) targeting the programmed cell death/programmed cell death ligand 1 (PD-1/PD-L1) pathway, has emerged as a promising therapy for these patients. However, identifying biomarkers predictive of response to nivolumab remains critical for optimizing treatment strategies. Previous studies have suggested that PD-L1 expression, as determined by the Combined Positive Score (CPS) and other clinical factors, may influence treatment outcome. This study aims to retrospectively examine whether CPS can be a biomarker by staining PD-L1 with 22 C3 antibody in R/MHNSCC patients treated with nivolumab.</p><p><strong>Methods: </strong>This retrospective study reviewed the medical records of R/MHNSCC patients treated with ICIs at Tokai University Hospital from April 2017 to December 2022. We examined the relationship between response rate to ICI therapy, PD-L1 staining, biomarkers, and survival. Statistical analyses included <i>t</i>-test, chi-square test, and Cox regression.</p><p><strong>Results: </strong>This study included 92 nivolumab-treated patients. Combined Positive Score was evaluable in 53 of these patients. Patients with a CPS of 15 or higher had better progression-free survival (PFS) (<i>P</i> = .0171), with a median PFS) of 13 months. In the Various Definitions analysis, cisplatin-sensitive patients also had good PFS (<i>P</i> = .0295). The cisplatin-sensitive patient population with a CPS of 15 or higher had the best PFS, with a median of 14 months (<i>P</i> = .006). There was no significant difference in overall survival (OS) by CPS value. Immune-related adverse events did not affect OS or PFS.</p><p><strong>Conclusions: </strong>CPS ⩾ 15 and cisplatin sensitivity are promising prognostic markers for nivolumab therapy in R/MHNSCC. Considering these biomarkers in patient selection could maximize the therapeutic benefits of nivolumab. This finding may help to optimize ICI therapy strategies.</p>","PeriodicalId":48591,"journal":{"name":"Clinical Medicine Insights-Oncology","volume":"18 ","pages":"11795549241290030"},"PeriodicalIF":1.9,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11490953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Clinical Implications of RPL3 Presence in BRCA-Associated Cancers: Unraveling the Interplay With Cancer Immunity.","authors":"Linyi Wang, Minlong Chen, Zhaosheng Ma, Hanqian Zeng, Bojian Xie, Shiwen Xu","doi":"10.1177/11795549241285387","DOIUrl":"10.1177/11795549241285387","url":null,"abstract":"<p><strong>Background: </strong>Few studies have explored the expression profile of RPL3 in breast cancer (BRCA). Our research provided an in-depth analysis of RPL3 expression patterns in BRCA, highlighting its significance for therapy prediction and prognosis.</p><p><strong>Methods: </strong>RPL3 was notably elevated in malignant cells, and its expression level was closely associated with tumor size and overall survival outcomes. Our study also identified RPL3-related terms and pathways and revealed a strong correlation between RPL3 expression and breast carcinoma immunity, demonstrating inconsistent expression levels in various immune cell lines. In addition, we examined the relationship between RPL3 expression and tumor mutational burden (TMB) in BRCA. To assess the clinical implications of BRCA chemotherapy, we investigated the correlation between RPL3 expression levels and drug sensitivity.</p><p><strong>Results: </strong>Our findings suggest that RPL3 plays a critical role in the BRCA process and is associated with immune infiltration, indicating its potential as a novel immunotherapy target in BRCA treatment.</p><p><strong>Conclusions: </strong>In summary, our research underscores the importance of RPL3 expression levels in tumorigenesis and its potential for guiding BRCA immunotherapy.</p>","PeriodicalId":48591,"journal":{"name":"Clinical Medicine Insights-Oncology","volume":"18 ","pages":"11795549241285387"},"PeriodicalIF":1.9,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11488323/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-World Data Presenting the Descriptive Analysis of the Use of Tyrosine Kinase Inhibitors (TKIs) Among Metastatic Non-Small-Cell Lung Cancer (mNSCLC) Patients in Qatar: A Nationwide Retrospective Cohort Study.","authors":"Rawan Dawoud, Harman Saman, Kakil Rasul, Farah Jibril, Arwa Sahal, Randa Al-Okka, Yaser Mahfouz, Nabil E Omar, Anas Hamad, Reyad Mohsen, Aladdin Kanbour, Naim Battikh, Prem Chandra, Shereen Elazzazy","doi":"10.1177/11795549241272490","DOIUrl":"https://doi.org/10.1177/11795549241272490","url":null,"abstract":"<p><strong>Background: </strong>There has been significant improvement in treating metastatic non-small-cell lung cancer (mNSCLC) over the past 2 decades. The aim of this study is to describe the use of tyrosine kinase inhibitors (TKIs) in Qatar. This study focuses on the objective response rate (ORR) and reported adverse drug events (ADEs) of TKIs used for the management of patients with mNSCLC.</p><p><strong>Methods: </strong>This is a descriptive retrospective cohort study. All non-small-cell lung cancers (NSCLCs) with epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) mutations who received TKIs between 2015 and 2019 in Qatar were included. The TKIs used during this period include EGFR inhibitors such as afatinib, erlotinib, gefitinib, and osimertinib and ALK inhibitors such as alectinib and crizotinib. The response on each TKI was identified by reporting the ORR (as the sum of the complete response [CR] and the partial response [PR]), in addition stable disease (SD) and disease progression (DP) were reported. While ADEs were reported using the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE).</p><p><strong>Results: </strong>A total of 63 patients were included, of which 36 cases (57.1%) expressed EGFR mutation, and 27 patients (42.9%) expressed ALK rearrangement. The ORR in EGFR inhibitors was as follows: osimertinib 40%, gefitinib 33%, afatinib 22%, and erlotinib 18%. However, the response to the ALK-targeted therapy was 43% with alectinib and 40% with crizotinib. A total of 112 ADEs were reported. They were distributed as 63.4% (71 of 112) with the anti-EGFR and 36.6% (41 of 112) ADEs with the ALK inhibitors. In the anti-EGFR group, the most common types of ADEs were dermatological toxicity 30%, whereas, in the anti-ALK group, gastrointestinal toxicity was the most common (29%).</p><p><strong>Conclusions: </strong>The EGFR-targeted and ALK-targeted therapies appear to have acceptable clinical response rate and safety profile in our population. Close and frequent monitoring of adverse events is advised to ensure a good quality of life and prevent serious complications.</p>","PeriodicalId":48591,"journal":{"name":"Clinical Medicine Insights-Oncology","volume":"18 ","pages":"11795549241272490"},"PeriodicalIF":1.9,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11481063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}