American journal of cancer research最新文献

{"title":"Interstitial pneumonia development after chemotherapy in B-cell non-hodgkin's lymphoma patients: clinical profiles and risk factors.","authors":"Ruijuan Ma, Yuan Li, Shaoning Yin, Yuhuan Gao, Guimin Zhao","doi":"10.62347/BTGQ7302","DOIUrl":"https://doi.org/10.62347/BTGQ7302","url":null,"abstract":"<p><p>Interstitial pneumonia (IP) is a significant adverse effect of chemotherapy in B-cell non-Hodgkin's lymphoma (NHL) patients. This study aimed to identify the clinical characteristics, risk factors, and treatment outcomes associated with IP in these patients. A retrospective review of 615 NHL patients treated at the Fourth Hospital of Hebei Medical University from 2016 to 2021 identified 50 patients with IP post-chemotherapy as the case group. A propensity score matched control group of 55 patients without pneumonia was established. Clinical profiles, risk factors, and treatment outcomes were evaluated. The IP incidence was 8.13% (50/615) in B-cell NHL patients. Multivariate analysis revealed liposomes, elevated lactate dehydrogenase (LDH), and erythrocyte sedimentation rate (ESR) as independent risk factors for IP. Receiver Operating Characteristic (ROC) curve analyses suggested that alterations in LDH and ESR could predict IP risk. The conclusion suggests that IP is associated with liposomal doxorubicin-induced lung injury and other cytotoxic chemotherapy, possibly due to Rituximab (RTX)-induced immune imbalance. Given the potential of IP with pulmonary infections, high-risk patients may need prophylactic antibiotics and appropriate corticosteroid therapy.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 9","pages":"4484-4494"},"PeriodicalIF":3.6,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11477814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PGC1α as a downstream effector of KDM5B promotes the progression of androgen receptor-positive and androgen receptor-negative prostate cancers.","authors":"Yuki Teramoto, Zhiming Yang, Takuo Matsukawa, Mohammad Amin Elahi Najafi, Takuro Goto, Hiroshi Miyamoto","doi":"10.62347/QWZY6886","DOIUrl":"https://doi.org/10.62347/QWZY6886","url":null,"abstract":"<p><p>PPARγ coactivator-1α (PGC1α), as a co-activator, is known to optimize the action of several transcription factors, including androgen receptor (AR). However, the precise functions of PGC1α in prostate cancer, particularly those via the non-AR pathways, remain poorly understood. Meanwhile, our bioinformatics search suggested that PGC1α could be a direct downstream target of lysine-specific demethylase 5B (KDM5B/JARID1B/PLU1). We herein aimed to investigate how PGC1α induced prostate cancer outgrowth. Immunohistochemistry in radical prostatectomy specimens showed that the levels of PGC1α expression were significantly higher in prostatic adenocarcinoma [H-score (mean ± SD): 179.0 ± 111.6] than in adjacent normal-appearing tissue (16.7 ± 29.9, <i>P</i><0.001) or high-grade prostatic intraepithelial neoplasia (79.0 ± 94.7, <i>P</i><0.001). Although there were no strong associations of PGC1α expression with tumor grade or stage, outcome analysis revealed that patients with high PGC1α (H-score of ≥200) tumor had a significantly higher risk of postoperative biochemical recurrence even in a multivariable setting (hazard ratio 5.469, <i>P</i>=0.004). In prostate cancer LNCaP and C4-2 cells, PGC1α silencing resulted in considerable reduction in the levels of prostate-specific antigen expression. Interestingly, PGC1α silencing inhibited the cell viability of not only AR-positive LNCaP/C4-2/22Rv1 lines but also AR-negative PC3/DU145 lines. Chromatin immunoprecipitation assay further revealed the binding of KDM5B to the promoter region of <i>PGC1α</i> in these lines. Additionally, treatment with a KDM5 inhibitor KDM5-C70 considerably reduced the expression of PGC1α and prostate-specific antigen, as well as the cell viability of all the AR-positive and AR-negative lines examined. PGC1α silencing or KDM5-C70 treatment also down-regulated the expression of phospho-JAK2 and phospho-STAT3 in both AR-positive and AR-negative cells. These findings suggest the involvement of PGC1α, as a downstream effector of KDM5B, in prostate cancer progression via both AR-dependent and AR-independent pathways. KDM5B-PGC1α is thus a potential therapeutic target for both androgen-sensitive and castration-resistant tumors. Meanwhile, PGC1α overexpression may serve as a useful prognosticator in those undergoing radical prostatectomy.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 9","pages":"4367-4377"},"PeriodicalIF":3.6,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11477833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Roles of clinical application of lenvatinib and its resistance mechanism in advanced hepatocellular carcinoma (Review).","authors":"Ganghui Ye, Meng Ye, Xiaofeng Jin","doi":"10.62347/UJVP4361","DOIUrl":"https://doi.org/10.62347/UJVP4361","url":null,"abstract":"<p><p>Lenvatinib (LEN) is a multi-target TKI, which plays a pivotal role in the treatment of advanced hepatocellular carcinoma (HCC). The inevitable occurrence of drug resistance still prevents curative potential and is deleterious for the prognosis, and a growing body of studies is accumulating, which have devoted themselves to unveiling its underlying resistance mechanism and made some progress. The dysregulation of crucial signaling pathways, non-coding RNA and RNA modifications were proven to be associated with LEN resistance. A range of drugs were found to influence LEN therapeutic efficacy. In addition, the superiority of LEN combination therapy has been shown to potentially overcome the limitations of LEN monotherapy in a series of research, and a range of promising indicators for predicting treatment response and prognosis have been discovered in recent years. In this review, we summarize the latest developments in LEN resistance, the efficacy and safety of LEN combination therapy as well as associated indicators, which may provide new insight into its resistance as well as ideas in the treatment of advanced HCC.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 9","pages":"4113-4171"},"PeriodicalIF":3.6,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11477829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Zeb1-Cxcl1 axis impairs the antitumor immune response by inducing M2 macrophage polarization in breast cancer.","authors":"Yang Ou, Hui-Min Jiang, Yan-Jing Wang, Qiu-Ying Shuai, Li-Xia Cao, Min Guo, Chun-Chun Qi, Zhao-Xian Li, Jie Shi, Hua-Yu Hu, Yu-Xin Liu, Si-Yu Zuo, Xiao Chen, Meng-Dan Feng, Yi Shi, Pei-Qing Sun, Hang Wang, Shuang Yang","doi":"10.62347/UAIS7070","DOIUrl":"https://doi.org/10.62347/UAIS7070","url":null,"abstract":"<p><p>Zeb1, a key epithelial-mesenchymal transition (EMT) regulator, has recently been found to be involved in M2 macrophage polarization in the tumor immune microenvironment, thereby promoting tumor development. However, the underlying mechanism of Zeb1-induced M2 macrophage polarization remains largely unexplored. To identify the potential role of Zeb1 in remodeling the tumor immune microenvironment in breast cancer, we crossed the floxed Zeb1 allele homozygously into PyMT mice to generate PyMT;<i>Zeb1^cKO</i> (MMTV-Cre;PyMT;<i>Zeb1^fl/fl</i> ) mice. We found that the recruitment of M2-type tumor-associated macrophages (TAMs) was significantly reduced in tumors from PyMT;<i>Zeb1^cKO</i> mice, and their tumor suppressive effects were weakened. Mechanistically, Zeb1 played a crucial role in transcriptionally promoting the production of Cxcl1 in tumor cells. In turn, Cxcl1 activated the Cxcr2-Jak-Stat3 pathway to induce M2 polarization of TAMs in a paracrine manner, which eventually led to T-cell inactivation and impaired the antitumor immune response in breast cancer. Our results collectively revealed an important role of Zeb1 in remodeling the tumor microenvironment, suggesting a novel therapeutic intervention for the treatment of advanced breast cancer.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 9","pages":"4378-4397"},"PeriodicalIF":3.6,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11477816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of opioids and mu-opioid receptors on oncologic metastasis.","authors":"Runjia Wang, Shuai Li, Bomin Wang, Gongming Wang, Hui Zheng","doi":"10.62347/SCLS3277","DOIUrl":"https://doi.org/10.62347/SCLS3277","url":null,"abstract":"<p><p>Opioids are the most effective and widely used treatments for acute and chronic pain in patients with cancer. This review focuses on the impact of opioids and mu-opioid receptors (MORs) on the stages of oncologic metastasis. Studies have shown that opioids can facilitate tumor progression and are related to a poor prognosis in patients with cancer. As the primary receptor for opioids, MORs play a significant role in regulating malignant tumor transformation and are involved in processes, such as proliferation, angiogenesis, epithelial-mesenchymal transition (EMT), circulating tumor cells (CTCs) and the tumor microenvironment (TME). While clinical trials have investigated the relationship between opioids and patient prognosis, further research is needed to clarify the relationship between opioids, MORs and metastasis.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 9","pages":"4236-4247"},"PeriodicalIF":3.6,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11477826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Attenuation of aggressive tumor progression of anaplastic thyroid cancer by p53.","authors":"Eunmi Hwang, Michael Kruhlak, Nathan Wong, Raj Chari, Takahito Kimura, Sheue-Yann Cheng","doi":"10.62347/KXJJ8824","DOIUrl":"https://doi.org/10.62347/KXJJ8824","url":null,"abstract":"<p><p>Anaplastic thyroid cancer (ATC) is the most aggressive thyroid cancer, with very limited treatment options. Mutations of p53 are associated with lethal outcomes of ATC. In this study, we tested the hypothesis that wild type p53 (WTp53) mitigates its aggressive progression. We used human 8505C cells (from human ATC tumors) as a model, harboring a BRAF^V600E mutation and single of mutated p53^C742G allele. We exogenously expressed WTp53 or mutant p53^C742G into 8505C cells (8505C-WTp53 or 8505C-MTp53, respectively). The expressed WTp53 inhibited cell proliferation, decreased cell migration, and induced apoptosis via induction of proapoptotic WTp53 target <i>BAX</i> and <i>PUMA</i> genes <i>in vitro</i>. Mouse xenograft studies showed suppression of tumors induced by 8505C-WTp53 but not by 8505C-MTp53 cells. Consistent with <i>in vitro</i> findings, WTp53 inhibited proliferation of tumor cells, evidenced by decreased proliferation marker Ki-67 in tumors. WTp53 also induced apoptosis in xenograft tumors as shown by increased cleaved caspase-3 proteins and pro-apoptotic regulators, BAX and PUMA. Single cells RNA-sequencing (scRNA-seq) of tumors induced by 8505C, 8505C-WTp53, and 8505C-MTp53 cells demonstrated differential expression gene (DEG) patterns between 8505C-WTp53 and 8505C tumors. DEGs analysis identified alteration of multiple pathways, leading to attenuating the oncogenic actions of mutant p53. The discovery of the suppression of TNFα via NFκB pathway topped the pathways list, resulting in subduing the deleterious inflammatory responses caused by mutant p53. Our findings that exogenously expressed WTp53 could counter act the oncogenic actions of p53 has heightened the feasibility of using CRISPR/Cas9 genome editing to modify the p53 alleles for potential treatment of ATC.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 9","pages":"4429-4444"},"PeriodicalIF":3.6,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11477845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nomogram-based prognostic model construction for progression to castration-resistant prostate cancer in patients with high tumor burden and osseous metastatic prostate cancer.","authors":"Yiheng Huang, Dan Yuan, Rongfeng Zeng, Fugui Wan, Yubo Tang, Yong Dong, Xiaorui Liu, Xitao Linghu, Bin Wang, Jiangang Pan, Fei Liang, Shuai Huang","doi":"10.62347/CWOS3653","DOIUrl":"https://doi.org/10.62347/CWOS3653","url":null,"abstract":"<p><p>This study aims to construct a Nomogram model to predict the risk of developing castration-resistant prostate cancer (CRPC) in patients with high tumor burden (HTB) and osseous metastatic prostate cancer (PCa), and to identify key prognostic factors. A retrospective analysis was conducted on patients with HTB and osseous metastatic PCa treated at The Sixth Affiliated Hospital, School of Medicine, South China University of Technology and the Second Affiliated Hospital of Guangzhou Medical University from January 2018 to February 2022. Patients' baseline data and laboratory indexes were collected. Cox regression analysis identified neural invasion (NI; P<0.001, HR: 2.371, 95% CI: 1.569-3.582), Gleason score (P=0.002, HR: 1.787, 95% CI: 1.241-2.573), initial PSA (P=0.004, HR: 1.677, 95% CI: 1.174-2.396), and lactate dehydrogenase (LDH; P<0.001, HR: 2.729, 95% CI: 1.855-4.014) as significant prognostic factors for progression to CRPC. The constructed Nomogram model exhibited high accuracy in predicting one- and two-year progression to CRPC, with external validation confirming its predictive performance. Time-dependent receiver operating characteristic (ROC) curves indicated that the areas under the curves (AUCs) of the model for one- and two-year progression to CRPC were 0.81 and 0.76, respectively. This model demonstrates high predictive performance, aiding clinical decision-making and providing personalized treatment strategies for patients with HTB and osseous metastatic PCa.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 9","pages":"4459-4471"},"PeriodicalIF":3.6,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11477824/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Construction of nomogram prediction model using heart rate and pulse perfusion variability index as predictors for hypotension in cervical cancer patients with spinal epidural anesthesia.","authors":"Chunping Xing, Gaolin Ji, Dongbo Zhang, Xiao Qin, Li Zhang, Cuiyun Yan","doi":"10.62347/WPPP9827","DOIUrl":"https://doi.org/10.62347/WPPP9827","url":null,"abstract":"<p><p>The prevention and treatment strategies for cervical cancer patients undergoing spinal epidural anesthesia have increasingly focused on early screening for high-risk factors associated with potential hypotension. We analyze the general conditions and preoperative examination results of 312 cervical cancer patients who received spinal epidural anesthesia, in order to identify independent risk factors for hypotension, assess their predictive efficacy, and construct a nomogram. 312 patients with cervical cancer received spinal epidural anesthesia were included in this study. Among them, 164 patients with hypotension after hysterectomy with spinal epidural anesthesia were in a hypotension group. Important risk predictors of hypotension after hysterectomy with spinal epidural anesthesia were identified using univariate and multivariate analyses, then a clinical nomogram was constructed. The predictive accuracy was assessed by unadjusted concordance index (C-index) and calibration plot. Univariate and multivariate regression analysis identified basal HR (≥95) (95% CI 0.831-0.900; P = 0.000) and basal PVI (95% CI 0.679-0.877; P = 0.000) were the independent risk factors for hypotension in cervical cancer patients with spinal epidural anesthesia. Those risk factors were used to construct a clinical predictive nomogram. The regression equation model based on the above factors was logit (P) = -6.820 + 0.216 * basal HR + basic PVI * 0.312. The calibration curves for hypotension risk revealed excellent accuracy of the predictive nomogram model. Decision curve analysis showed that the predictive model could be applied clinically when the threshold probability was 20 to 75%. We surmised that the basal HR values and PVI values are the independent risk factors for hypotension in cervical cancer patients with spinal epidural anesthesia. The construction of nomograms is beneficial in predicting the risk of hypotension in these patients.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 9","pages":"4398-4410"},"PeriodicalIF":3.6,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11477840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Uncovering the role of FXYD3 as a potential oncogene and early biomarker in pancreatic cancer.","authors":"Ke Xin Yee, Yu-Cheng Lee, Hieu Duc Nguyen, Ming-Yao Chen, Yi-Chun Ni, Yung-Fu Wu, Kuen-Haur Lee","doi":"10.62347/LUDE7524","DOIUrl":"https://doi.org/10.62347/LUDE7524","url":null,"abstract":"<p><p>Pancreatic cancer is an aggressive cancer with silent symptoms and high mortality with less than 11% of the 5-year survival rate. Until now, the significance of genes as clinical biomarkers in the early stages of pancreatic cancer has not been fully understood. Hence, this study aims to reveal the significant genes in the early stages of pancreatic cancer using bioinformatic analysis and <i>in vitro</i> experiments, and to serve as clinical biomarkers for early detection. We used Cancer RNA-Seq Nexus database and identified one tumor suppressor gene (NAGK), and five oncogenes (FXYD3, ACTR1A, B3GNT3, SIGIRR, and EXOC1) that are significant in the early stages of pancreatic cancer. The expression of NAGK, FXYD3, ACTR1A, B3GNT3, SIGIRR, and EXOC1 were determined from the GEPIA, UALCAN, and HPA database. It has been shown that pancreatic cancer tumor dissemination is an event that can occur in early lesions, rather than being solely restricted in the developed primary tumor. Thus, the six hub genes that were differentially expressed between stage I and stage II of primary pancreatic cancer tumors were compared to metastasis-related genes (1938 genes) in the human cancer metastasis database (HCMDB), yielding two overlapped genes (B3GNT3 and FXYD3). To establish the expression correlation between these two specific genes with metastatic characteristics of the early stage of pancreatic cancer and migratory ability in pancreatic cancer cell lines, the expression patterns of B3GNT3 and FXYD3 were examined in four different migratory abilities of pancreatic cancer cell lines, including HPAC, BxPC-3, AsPC-1, and PANC-1, as well as the normal pancreatic duct epithelial cell line HPDE6-C7. The results displayed that the expression of the FXYD3 gene was dramatically increased with the migratory ability enhanced of four pancreatic cancer cell lines. Thus, in the follow-up study, we will demonstrate the functional role of FXYD3 in pancreatic cancer tumorigenesis. This study revealed that the FXYD3 may act as a significant oncogene in the early stage of pancreatic cancer.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 9","pages":"4353-4366"},"PeriodicalIF":3.6,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11477818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Utidelone-based therapy in advanced or metastatic solid tumors after failure of standard therapies: a prospective, multicenter, single-arm trial.","authors":"Guanglei Qiao, Zimei Liu, Honghua Ding, Hongmin Lu, Feng Lin, Yang Shi, Leizhen Zheng, Mei Wang, Ying Chen, Zhoufeng Deng, Liping Yu, Yan Zhang, Ying Yuan, Hongjian Lin, Lijun Ma, Jianjun Zhang","doi":"10.62347/OLES9793","DOIUrl":"https://doi.org/10.62347/OLES9793","url":null,"abstract":"<p><p>Treatment options are limited for tumors after failure of standard therapies. Utidelone (UTD1), a novel microtubule stabilizer, given via 5 days intermittent infusion, has demonstrated high activity in heavily pretreated metastatic breast cancer, while its efficacy in other cancers was unclear. Peripheral neuropathy is a common and severe adverse event (AE) of UTD1. We performed a prospective, multicenter, single-arm trial (ChiCTR2300074299) to evaluate the efficacy and safety of UTD1 with a changed administration mode in patients with advanced or metastatic solid tumors after failure of standard therapies. UTD1 (150 mg/m², alone or in combination with other anticancer agents) was administrated via 120 h continuous intravenous infusion every 21 days until disease progression or intolerable toxicity. A total of 50 patients were enrolled and analyzed, including 20 breast cancer patients, 11 gynecological cancer patients, 8 gastrointestinal cancer patients, 6 lung cancer patients, and 5 patients with other solid tumors. The overall median progression-free survival (PFS) was 4 months, the overall objective response rate and disease control rate were 20% and 66%, respectively, and the median overall survival was not reached. Most of the AEs were grade 1 or 2 and were manageable and reversible, the rate of grade ≥3 AEs including peripheral neuropathy was 4%. This study demonstrated a promising anti-tumor activity of UTD1 in patients with advanced or metastatic solid tumors after failure of the standard therapies. Moreover, 120 h continuous intravenous infusion was a more tolerable administration mode than 5 days intermittent infusion, and worthy of further study.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 9","pages":"4514-4522"},"PeriodicalIF":3.6,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11477828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}