Cancer pathogenesis and therapy最新文献

{"title":"Clinical features and prognostic analysis of the blastoid variant of mantle cell lymphoma: An analysis of 20 patients from two centers","authors":"Sai Huang , Shaomei Liu , Hongmei Jing , Ping Chen , Lili Dong , Xiaoyu Hao , Jian Bo , Lu Sun , Yu Zhao","doi":"10.1016/j.cpt.2023.10.007","DOIUrl":"10.1016/j.cpt.2023.10.007","url":null,"abstract":"","PeriodicalId":93920,"journal":{"name":"Cancer pathogenesis and therapy","volume":"2 1","pages":"Pages 62-64"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949713223000897/pdfft?md5=fc420b70a7df102d6afbbf52030e46e3&pid=1-s2.0-S2949713223000897-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136127418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reversal of the immunosuppressive tumor microenvironment via platinum-based neoadjuvant chemotherapy in cervical cancer","authors":"Xue Feng ,&nbsp;Xiaolin Meng ,&nbsp;Dihong Tang ,&nbsp;Shuaiqingying Guo ,&nbsp;Qiuyue Liao ,&nbsp;Jing Chen ,&nbsp;Qin Xie ,&nbsp;Fengyuan Liu ,&nbsp;Yong Fang ,&nbsp;Chaoyang Sun ,&nbsp;Yingyan Han ,&nbsp;Jihui Ai ,&nbsp;Kezhen Li","doi":"10.1016/j.cpt.2023.07.003","DOIUrl":"10.1016/j.cpt.2023.07.003","url":null,"abstract":"<div><h3>Background</h3><p>Immunotherapy favors patients with tumors; however, only 3–26.3% of patients with cervical cancer benefit from single-agent immune checkpoint inhibitors. Combined immunotherapy and chemotherapy has been explored against tumor; however, the combination remains controversial. This study aimed to investigate the tumor immune microenvironment (TIME) and the effects of platinum-based neoadjuvant chemotherapy (NACT) in cervical cancer to identify the clinical value of combining chemotherapy with immunotherapy.</p></div><div><h3>Methods</h3><p>Multiplex immunohistochemistry (IHC) with 11 markers (cluster of differentiation [CD]3, CD8, CD4, CD11c, CD68, forkhead box P3 [Foxp3], programmed cell death 1 [PD-1], programmed cell death 1 ligand 1 [PD-L1], indoleamine 2,3-dioxygenase [IDO], cyclin-dependent kinase inhibitor 2A [p16], and cytokeratin [CK]) was performed to evaluate TIME from 108 matched pre- and post-NACT cervical cancer samples. The mechanism of antitumor immunity triggered by NACT was explored using RNA sequencing (RNA-seq) from four paired samples and subsequently verified in 41 samples using IHC.</p></div><div><h3>Results</h3><p>The infiltration rate of the CD8⁺ T cells in treatment-naive cervical cancer was 0.73%, and those of Foxp3⁺ regulatory T cells (Tregs) and IDO⁺ cells were 0.87% and 17.15%, respectively. Moreover, immunoreactive T cells, dendritic cells, and macrophages were more in the stromal than the intratumor region. NACT increased dendritic, CD3⁺ T, CD8⁺ T, and CD4⁺ T cells and decreased Tregs. The aforementioned alterations occurred predominantly in the stromal region and were primarily in responders. Non-responders primarily showed decreased Tregs and no increase in CD8⁺ T or dendritic cell infiltration. Furthermore, dendritic cells interacted more closely with CD3⁺ T cells after NACT, an effect primarily observed in responders. RNA-seq data revealed activation of the antigen receptor-mediated signaling pathway and upregulation of major histocompatibility complex (MHC) I and MHC II after chemotherapy, validated using IHC.</p></div><div><h3>Conclusions</h3><p>NACT can reduce Tregs, and when tumor cells are effectively killed, antigen presentation is enhanced, subsequently activating antitumor immunity finitely. Our study provides the molecular characteristics and theoretical basis for the simultaneous or sequential combination of platinum-based NACT and immunotherapy for cervical cancer.</p></div>","PeriodicalId":93920,"journal":{"name":"Cancer pathogenesis and therapy","volume":"2 1","pages":"Pages 38-49"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949713223000460/pdfft?md5=9c95ed1180f2b1c613ea514217561b19&pid=1-s2.0-S2949713223000460-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83898936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and toxicity of anlotinib plus camrelizumab versus anlotinib plus S-1 as second-line therapy for advanced esophageal squamous cell carcinoma: A real-world retrospective study","authors":"","doi":"10.1016/j.cpt.2023.12.003","DOIUrl":"10.1016/j.cpt.2023.12.003","url":null,"abstract":"<div><h3>Background</h3><div>No data exist on the efficacy and safety of anlotinib plus camrelizumab doublet as second-line therapy for advanced esophageal squamous cell carcinoma (ESCC). Although anlotinib and the programmed death-1 (PD-1) inhibitor camrelizumab are used as treatments for ESCC, the combined use of anlotinib and camrelizumab as a second-line therapy has not been reported. Therefore, this study explored the efficacy and toxicity of anlotinib plus camrelizumab as second-line therapy for advanced ESCC.</div></div><div><h3>Methods</h3><div>Fifty-eight patients with advanced ESCC undergoing second-line therapy, either with anlotinib plus camrelizumab or anlotinib plus S-1, were enrolled and retrospectively analyzed at Jiangsu Province Hospital of Chinese Medicine from January 2020 to December 2021. The primary endpoint was progression-free survival (PFS), with secondary endpoints including the objective response rate (ORR), disease control rate (DCR), and assessment of toxicity.</div></div><div><h3>Results</h3><div>In patients with advanced ESCC, the anlotinib plus camrelizumab group (<em>N</em> = 32) exhibited longer PFS (8.00 <em>vs.</em> 4.53 months, <em>P</em> &lt; 0.001), higher ORR (28.1 <em>vs.</em> 19.2%, <em>P</em> = 0.431), and higher DCR (87.5 <em>vs.</em> 65.4%, <em>P</em> = 0.045) than those in the anlotinib plus S-1 group (<em>N</em> = 26). Treatment-related adverse events (TRAEs) were predominantly grade 1/2 in both groups, with a higher incidence of grade 1/2 skin toxicity in patients treated with anlotinib plus camrelizumab (<em>P</em> = 0.033). Two patients (6.3%) developed grade 1/2 immune-related pneumonia. The incidence of grade 3/4 TRAEs did not differ significantly between the two groups. Multivariable Cox regression analysis identified that the drug regimen (<em>P</em> &lt; 0.001), Eastern Cooperative Oncology Group performance status (<em>P</em> = 0.008), and differentiation grade (<em>P</em> = 0.008) were independent prognostic factors for PFS.</div></div><div><h3>Conclusions</h3><div>Anlotinib plus camrelizumab exhibited promising antitumor efficacy and manageable toxicity when used as a second-line treatment for advanced ESCC.</div></div>","PeriodicalId":93920,"journal":{"name":"Cancer pathogenesis and therapy","volume":"2 4","pages":"Pages 276-284"},"PeriodicalIF":0.0,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949713223001064/pdfft?md5=795f6848529b655d76ae2f3a7a24bf94&pid=1-s2.0-S2949713223001064-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139015429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transforming growth factor-β (TGF-β) signaling pathway-related genes in predicting the prognosis of colon cancer and guiding immunotherapy","authors":"","doi":"10.1016/j.cpt.2023.12.002","DOIUrl":"10.1016/j.cpt.2023.12.002","url":null,"abstract":"<div><h3>Background</h3><div>Colon cancer is a malignant tumor with high malignancy and a low survival rate whose heterogeneity limits systemic immunotherapy. Transforming growth factor-β (TGF-β) signaling pathway-related genes are associated with multiple tumors, but their role in prognosis prediction and tumor microenvironment (TME) regulation in colon cancer is poorly understood. Using bioinformatics, this study aimed to construct a risk prediction signature for colon cancer, which may provide a means for developing new effective treatment strategies.</div></div><div><h3>Methods</h3><div>Using consensus clustering, patients in The Cancer Genome Atlas (TCGA) with colon adenocarcinoma were classified into several subtypes based on the expression of TGF-β signaling pathway-related genes, and differences in survival, molecular, and immunological TME characteristics and drug sensitivity were examined in each subtype. Ten genes that make up a TGF-β-related predictive signature were found by least absolute shrinkage and selector operation (LASSO) regression using colon cancer data from the TCGA database and confirmed using a Gene Expression Omnibus (GEO) dataset. A nomogram incorporating risk scores and clinicopathologic factors was developed to stratify the prognosis of patients with colon cancer for accurate clinical diagnosis and therapy.</div></div><div><h3>Results</h3><div>Two TGF-β subtypes were identified, with the TGF-β-high subtype being associated with a poorer prognosis and superior sensitivity to immunotherapy. Mutation analyses showed a high incidence of gene mutations in the TGF-β-high subtype. After completing signature construction, patients with colon cancer were categorized into high- and low-risk subgroups based on the median risk score of the TGF-β-related predictive signature. The risk score exhibited superior predictive performance relative to age, gender, and stage, as evidenced by its AUC of 0.686. Patients in the high-risk subgroup had higher levels of immunosuppressive cell infiltration and immune checkpoints in the TME, suggesting that these patients had better responses to immunotherapy.</div></div><div><h3>Conclusions</h3><div>Patients with colon cancer were divided into two subtypes with different survival and immune characteristics using consensus clustering analysis based on TGF-β signaling pathway-related genes. The constructed risk prediction signature may show promise as a biomarker for evaluating the prognosis of colon cancer, with potential utility for screening individuals for immunotherapy.</div></div>","PeriodicalId":93920,"journal":{"name":"Cancer pathogenesis and therapy","volume":"2 4","pages":"Pages 299-313"},"PeriodicalIF":0.0,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949713223001052/pdfft?md5=16ae2f851b11cba145a4d55af4521b5c&pid=1-s2.0-S2949713223001052-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138991461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intraoperative glioblastoma surgery-current challenges and clinical trials: An update","authors":"","doi":"10.1016/j.cpt.2023.11.006","DOIUrl":"10.1016/j.cpt.2023.11.006","url":null,"abstract":"<div><div>Surgical excision is an important part of the multimodal therapy strategy for patients with glioblastoma, a very aggressive and invasive brain tumor. While major advances in surgical methods and technology have been accomplished, numerous hurdles remain in the field of glioblastoma surgery. The purpose of this literature review is to offer a thorough overview of the current challenges in glioblastoma surgery. We reviewed the difficulties associated with tumor identification and visualization, resection extent, neurological function preservation, tumor margin evaluation, and inclusion of sophisticated imaging and navigation technology. Understanding and resolving these challenges is critical in order to improve surgical results and, ultimately, patient survival.</div></div>","PeriodicalId":93920,"journal":{"name":"Cancer pathogenesis and therapy","volume":"2 4","pages":"Pages 256-267"},"PeriodicalIF":0.0,"publicationDate":"2023-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949713223000952/pdfft?md5=5ae675a3e185e13e0d0a139e5567f4d1&pid=1-s2.0-S2949713223000952-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138612898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Theories behind Bacillus Calmette-Guérin failure in high-risk non-muscle-invasive bladder cancer and update on current management","authors":"Hanna Maroof,&nbsp;Louise Paramore,&nbsp;Ahmed Ali","doi":"10.1016/j.cpt.2023.11.004","DOIUrl":"10.1016/j.cpt.2023.11.004","url":null,"abstract":"<div><p>Bladder cancer encapsulates a wide spectrum of disease severities, with non-muscle invasive bladder cancer (NMIBC) representing an entirely different entity from muscle-invasive disease. Bacillus Calmette-Guérin (BCG) is one of the most successful intravesical treatment methods for patients diagnosed. However, a considerable proportion of patients fail to respond to BCG treatment. Given the propensity for recurrence in patients with high-risk bladder cancer, these patients present with surgical dilemmas. There is currently no gold standard for salvage treatment post-BCG failure or unified definition as to what that means. In this review, we discuss the mechanisms of action and pathophysiology of BCG, potential theories behind BCG failure, and the scope of novel treatments for this surgical conundrum.</p></div>","PeriodicalId":93920,"journal":{"name":"Cancer pathogenesis and therapy","volume":"2 2","pages":"Pages 74-80"},"PeriodicalIF":0.0,"publicationDate":"2023-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949713223000939/pdfft?md5=321d8ec7409ea20962b56be34ebd37a3&pid=1-s2.0-S2949713223000939-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139301658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Co-culture models for investigating cellular crosstalk in the glioma microenvironment","authors":"","doi":"10.1016/j.cpt.2023.11.002","DOIUrl":"10.1016/j.cpt.2023.11.002","url":null,"abstract":"<div><div>Glioma is the most prevalent primary malignant tumor in the central nervous system (CNS). It represents a diverse group of brain malignancies characterized by the presence of various cancer cell types as well as an array of noncancerous cells, which together form the intricate glioma tumor microenvironment (TME). Understanding the interactions between glioma cells/glioma stem cells (GSCs) and these noncancerous cells is crucial for exploring the pathogenesis and development of glioma. To invesigate these interactions requires <em>in vitro</em> co-culture models that closely mirror the actual TME <em>in vivo</em>. In this review, we summarize the two- and three-dimensional <em>in vitro</em> co-culture model systems for glioma-TME interactions currently available. Furthermore, we explore common glioma-TME cell interactions based on these models, including interactions of glioma cells/GSCs with endothelial cells/pericytes, microglia/macrophages, T cells, astrocytes, neurons, or other multi-cellular interactions. Together, this review provides an update on the glioma-TME interactions, offering insights into glioma pathogenesis.</div></div>","PeriodicalId":93920,"journal":{"name":"Cancer pathogenesis and therapy","volume":"2 4","pages":"Pages 219-230"},"PeriodicalIF":0.0,"publicationDate":"2023-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949713223000915/pdfft?md5=4f95c308ede234e85c3fe23111757339&pid=1-s2.0-S2949713223000915-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135510149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of indoleamine 2, 3-dioxygenase 1 in immunosuppression of breast cancer","authors":"","doi":"10.1016/j.cpt.2023.11.001","DOIUrl":"10.1016/j.cpt.2023.11.001","url":null,"abstract":"<div><div>Breast cancer (BC) contributes greatly to global cancer incidence and is the main cause of cancer-related deaths among women globally. It is a complex disease characterized by numerous subtypes with distinct clinical manifestations. Immune checkpoint inhibitors (ICIs) are not effective in all patients and have been associated with tumor resistance and immunosuppression. Because amino acid (AA)-catabolizing enzymes have been shown to regulate immunosuppressive effects, this review investigated the immunosuppressive roles of indoleamine 2,3-dioxygenase 1 (IDO1), a tryptophan (Trp)-catabolizing enzyme, which is overexpressed in various metastatic tumors. It promotes immunomodulatory effects by depleting Trp in the regional microenvironment. This leads to a reduction in the number of immunogenic immune cells, such as effector T and natural killer (NK) cells, and an increase in tolerogenic immune cells, such as regulatory T (Treg) cells. The BC tumor microenvironment (TME) establishes a supportive niche where cancer cells can interact with immune cells and neighboring endothelial cells and is thus a feasible target for cancer therapy. In many immunological contexts, IDO1 regulates immune control by causing regional metabolic changes in the TME and tissue environment, which may further affect the maturation of systemic immunological tolerance. In the development of effective treatment targets and approaches, it is essential to understand the immunomodulatory effects exerted by AA-catabolizing enzymes, such as IDO1, on the components of the TME.</div></div>","PeriodicalId":93920,"journal":{"name":"Cancer pathogenesis and therapy","volume":"2 4","pages":"Pages 246-255"},"PeriodicalIF":0.0,"publicationDate":"2023-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949713223000903/pdfft?md5=c3bdcb70f7807d28f075422bcdcbd40b&pid=1-s2.0-S2949713223000903-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135510357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of utidelone for the treatment of patients with locally advanced or metastatic non-small-cell lung cancer who have failed standard second-line treatment: A phase 2 clinical trial (BG01-1801)","authors":"Yuankai Shi ,&nbsp;Gongyan Chen ,&nbsp;Yanqiu Zhao ,&nbsp;Jing Zhao ,&nbsp;Lin Lin","doi":"10.1016/j.cpt.2023.10.006","DOIUrl":"10.1016/j.cpt.2023.10.006","url":null,"abstract":"<div><h3>Background</h3><p>Chemotherapy remains the standard-of-care for many patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC), but acquired resistance presents challenges. The aim of this open-label, multicenter phase 2 clinical trial was to determine the efficacy and safety of utidelone, a novel genetically engineered epothilone analog and microtubule-stabilizing agent, as a third- or later-line treatment for locally advanced or metastatic NSCLC.</p></div><div><h3>Methods</h3><p>Patients who had failed standard second-line treatment (including platinum-containing chemotherapy or targeted therapy) received utidelone (40 mg/m² via intravenous injection daily, day 1–5) every 21 days. The primary endpoint was the objective response rate (ORR). Secondary endpoints were the duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety.</p></div><div><h3>Results</h3><p>From March 12, 2019 to January 18, 2021, 26 pretreated patients with locally advanced or metastatic NSCLC (100% of patients had received prior platinum and 65.4% patients had received prior taxane treatment) were enrolled (80.8% of patients had adenocarcinoma). At baseline, nine (34.6%) patients had received second-line treatment, 10 (38.5%) patients had received third-line treatment, and seven (26.9%) patients had received fourth- or later-line treatment. By the data cut-off date of August 10, 2021, the median follow-up was 7.49 months (range, 1.4–26.7 months). The ORR was 15.4% (95% confidence interval [CI], 4.4%–34.9%) in the intention-to-treat (ITT) cohort (<em>N</em> = 26) and 19.0% (95% CI, 5.4%–41.9%) in the per-protocol (PP) cohort (<em>N</em> = 21). The disease control rate was 69.2% (95% CI, 48.2%–85.7%) and 81.0% (95% CI, 58.1%–94.6%) in the ITT and PP cohorts, respectively. The median DoR was 4.1 months (95% CI, 3.1–5.1 months) in the ITT cohort. The median PFS was 4.37 months (95% CI, 2.50–5.29 months) in the ITT cohort and 4.37 months (95% CI, 2.50–9.76 months) in the PP cohort. The median OS was not reached, and the 12-month OS rate was 69% (95% CI, 45.1%–84.1%). Grade 3/4 treatment-emergent adverse events occurred in 38.5% of patients, and the most common was peripheral neuropathy (23.1%, all Grade 3), which was manageable with dose modifications.</p></div><div><h3>Conclusions</h3><p>In this clinical trial, utidelone showed promising efficacy and had a manageable safety profile. Further clinical studies are warranted to confirm its role in NSCLC treatment.</p></div><div><h3>Trial registration</h3><p>No.NCT03693547; <span>https://classic.clinicaltrials.gov</span><svg><path></path></svg>.</p></div>","PeriodicalId":93920,"journal":{"name":"Cancer pathogenesis and therapy","volume":"2 2","pages":"Pages 103-111"},"PeriodicalIF":0.0,"publicationDate":"2023-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949713223000885/pdfft?md5=4f7f4f771b7361e58a706b4ed2e5e404&pid=1-s2.0-S2949713223000885-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136127651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Next-generation sequencing reveals relapse and leukemia-free survival risks in newly diagnosed acute myeloid leukemia treated with CAG regimen combined with decitabine","authors":"Sai Huang ,&nbsp;Peng Chen ,&nbsp;Lu Wang ,&nbsp;Lingmin Xu ,&nbsp;Nan Wang ,&nbsp;Fei Li ,&nbsp;Liping Dou ,&nbsp;Daihong Liu","doi":"10.1016/j.cpt.2023.10.002","DOIUrl":"10.1016/j.cpt.2023.10.002","url":null,"abstract":"<div><h3>Background</h3><p>Acute myeloid leukemia (AML) is a heterogeneous hematopoietic malignancy whose prognosis is associated with several biomarkers. Decitabine, a deoxyribonucleic acid (DNA) methyltransferase (DNMT) inhibitor, combined with cytarabine, aclarubicin hydrochloride, and granulocyte colony-stimulating factor (DCAG), has been used in patients newly diagnosed with AML. This regimen has been especially used in older and fragile patients who are immunocompromised or have co-morbidities, as well as those with specific gene mutations. However, the integration of molecular risk stratification and treatment guidance for the DCAG regimen has not been well defined. Therefore, this study aimed to investigate the genetic mutations associated with AML and establish appropriate treatment strategies for patients newly diagnosed with AML.</p></div><div><h3>Methods</h3><p>This study analyzed the clinical data and genetic mutations based on next-generation sequencing (NGS) in 124 newly diagnosed patients with AML who received the DCAG regimen at the People's Liberation Army (PLA) General Hospital from January 2008 to August 2020. Factors associated with the cumulative incidence of relapse (CIR) and leukemia-free survival (LFS) in patients newly diagnosed with AML were analyzed.</p></div><div><h3>Results</h3><p>The most adverse prognosis of DCAG-treated patients was observed in those with <em>FLT3-ITD, KIT, PTPN11, GATA2,</em> or <em>IDH1</em> mutations during univariable analysis, whereas <em>PTPN11</em> mutation was solely significant in multivariable analysis, with an increased likelihood of CIR (<em>P</em> = 0.001) and reduced LFS duration (<em>P</em> = 0.077). Hyperleukocytosis was maintained as an independent risk factor for increased CIR risk (<em>P</em> = 0.044) and decreased LFS duration (<em>P</em> = 0.042) in multivariable analysis. In this study, we validated the risk classification of patients with AML receiving an epigenetic modifier-based induction regimen across a broad age range.</p></div><div><h3>Conclusion</h3><p>NGS demonstrated a dismal overall outcome in patients with the rare <em>PTPN11</em> mutations, indicating the need for new therapies that target this high-risk subtype of AML. These results offer a potential molecular stratification and treatment guidance for patients with AML.</p></div>","PeriodicalId":93920,"journal":{"name":"Cancer pathogenesis and therapy","volume":"2 2","pages":"Pages 112-120"},"PeriodicalIF":0.0,"publicationDate":"2023-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949713223000848/pdfft?md5=13d16b5f18f63a5affe5cfcce3185123&pid=1-s2.0-S2949713223000848-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135706432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}