Cancer pathogenesis and therapy最新文献

{"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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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}

{"title":"BRAF-testing medical education needs in Latin America","authors":"João Mauricio Castaldelli-Maia ,&nbsp;Gislaine Koch Gimenes ,&nbsp;Giuliana Perrotte ,&nbsp;Stefani Gonzalez ,&nbsp;Ainur Okassova ,&nbsp;Karina Malvido ,&nbsp;Julio Torales","doi":"10.1016/j.cpt.2023.07.002","DOIUrl":"https://doi.org/10.1016/j.cpt.2023.07.002","url":null,"abstract":"","PeriodicalId":93920,"journal":{"name":"Cancer pathogenesis and therapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49710437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cover","authors":"","doi":"10.1016/S2949-7132(23)00061-7","DOIUrl":"https://doi.org/10.1016/S2949-7132(23)00061-7","url":null,"abstract":"","PeriodicalId":93920,"journal":{"name":"Cancer pathogenesis and therapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49705471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RNA splicing alterations in lung cancer pathogenesis and therapy","authors":"Yueren Yan ,&nbsp;Yunpeng Ren ,&nbsp;Yufang Bao ,&nbsp;Yongbo Wang","doi":"10.1016/j.cpt.2023.04.004","DOIUrl":"https://doi.org/10.1016/j.cpt.2023.04.004","url":null,"abstract":"<div><p>RNA splicing alterations are widespread and play critical roles in cancer pathogenesis and therapy. Lung cancer is highly heterogeneous and causes the most cancer-related deaths worldwide. Large-scale multi-omics studies have not only characterized the mutational landscapes but also discovered a plethora of transcriptional and post-transcriptional changes in lung cancer. Such resources have greatly facilitated the development of new diagnostic markers and therapeutic options over the past two decades. Intriguingly, altered RNA splicing has emerged as an important molecular feature and therapeutic target of lung cancer. In this review, we provide a brief overview of splicing dysregulation in lung cancer and summarize the recent progress on key splicing events and splicing factors that contribute to lung cancer pathogenesis. Moreover, we describe the general strategies targeting splicing alterations in lung cancer and highlight the potential of combining splicing modulation with currently approved therapies to combat this deadly disease. This review provides new mechanistic and therapeutic insights into splicing dysregulation in cancer.</p></div>","PeriodicalId":93920,"journal":{"name":"Cancer pathogenesis and therapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49705406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}