Cancer Science最新文献

{"title":"Salivary metabolomic biomarkers for esophageal and gastric cancers by liquid chromatography–mass spectrometry","authors":"Kosuke Nakane,&nbsp;Koichi Yagi,&nbsp;Sho Yajima,&nbsp;Sachiyo Nomura,&nbsp;Masahiro Sugimoto,&nbsp;Yasuyuki Seto","doi":"10.1111/cas.16256","DOIUrl":"10.1111/cas.16256","url":null,"abstract":"<p>Early detection of esophageal and gastric cancers is essential for patients' prognosis; however, optimal noninvasive screening tests are currently not available. Saliva is a biofluid that is readily available, allowing for frequent screening tests. Thus, we explored salivary diagnostic biomarkers for esophageal and gastric cancers using metabolomic analyses. Saliva samples were collected from patients with esophageal (<i>n</i> = 50) and gastric cancer (<i>n</i> = 63), and patients without cancer as controls (<i>n</i> = 20). Salivary metabolites were analyzed by liquid chromatography–mass spectrometry to identify salivary biomarkers. We also examined the metabolic profiles of gastric cancer tissues and compared them with the salivary biomarkers. The sensitivity of the diagnostic models based on salivary biomarkers was assessed by comparing it with that of serum tumor markers. Additionally, using postoperative saliva samples collected from patients with gastric cancer, we analyzed the changes in the biomarkers' concentrations before and after surgery. Cytosine was detected as a salivary biomarker for gastric cancer, and cytosine, 2-oxoglutarate, and arginine were detected as salivary biomarkers for esophageal cancer. Cytidine, a cytosine nucleotide, showed decreased concentrations in gastric cancer tissues. The sensitivity of the diagnostic models for esophageal and gastric cancers was 66.0% and 47.6%, respectively, while that of serum tumor markers was 40%. Salivary cytosine concentration increased significantly postoperatively relative to the preoperative value. In summary, we identified salivary biomarkers for esophageal and gastric cancers, which showed diagnostic sensitivity at least comparable to that of serum tumor markers. Salivary metabolomic tests could be promising screening tests for these types of cancer.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"115 9","pages":"3089-3098"},"PeriodicalIF":4.5,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.16256","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141617468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FOXM1/DEPDC1 feedback loop promotes hepatocarcinogenesis and represents promising targets for cancer therapy","authors":"Teng Wei,&nbsp;Chenquan Zeng,&nbsp;Qineng Li,&nbsp;Zhiyuan Xiao,&nbsp;Leisheng Zhang,&nbsp;Qiangnu Zhang,&nbsp;Lili Ren","doi":"10.1111/cas.16273","DOIUrl":"10.1111/cas.16273","url":null,"abstract":"<p><i>Forkhead box M1</i> (FOXM1) is a key regulator of mitosis and is identified as an oncogene involved in several kinds of human malignancies. However, how it induces carcinogenesis and related therapeutic approaches remains not fully understood. In this study, we aimed to identify a regulatory axis involving FOXM1 and its target gene <i>DEP domain containing 1</i> (DEPDC1) and investigate their biological functions. FOXM1 bound to the promoter and transcriptionally induced DEPDC1 expression, in turn, DEPDC1 physically interacted with FOXM1, promoted its nuclear translocation, and reinforced its transcriptional activities. The FOXM1/DEPDC1 axis was indispensable for cancer cells, as evidenced by the fact that DEPDC1 rescued cell growth inhibition caused by FOXM1 knockdown, and silencing DEPDC1 efficiently attenuated tumor growth in a murine hepatocellular carcinoma model. Furthermore, strong positive associations between FOXM1/DEPDC1 axis and poor clinical outcome were observed in human hepatocellular carcinoma samples, further indicating their significance for hepatocarcinogenesis. Finally, we attempted to exploit immunotherapy approaches to target the FOXM1/DEPDC1 axis. Several HLA-A24:02-restricted T-cell epitopes targeting FOXM1 or DEPDC1 were identified through bioinformatic analysis. Then, T cell receptor (TCR)-engineered T cells targeting FOXM1_262-270 or DEPDC1_294-302 were successfully established and proved to efficiently eradicate tumor cells. Our findings highlight the significance of the FOXM1/DEPDC1 axis in the process of oncogenesis and indicate their potential as immunotherapy targets.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"115 9","pages":"3041-3053"},"PeriodicalIF":4.5,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.16273","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141617466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nucleocytoplasmic β-catenin expression contributes to neuroendocrine differentiation in muscle invasive bladder cancer","authors":"Burcu Akman,&nbsp;Ahmet Bursalı,&nbsp;Mustafa Gürses,&nbsp;Aslı Suner,&nbsp;Gökhan Karakülah,&nbsp;Uğur Mungan,&nbsp;Kutsal Yörükoğlu,&nbsp;Serap Erkek-Ozhan","doi":"10.1111/cas.16275","DOIUrl":"10.1111/cas.16275","url":null,"abstract":"<p>Bladder cancers are heterogeneous in nature, showing diverse molecular profiles and histopathological characteristics, which pose challenges for diagnosis and treatment. However, understanding the molecular basis of such heterogeneity has remained elusive. This study aimed to elucidate the molecular landscape of neuroendocrine-like bladder tumors, focusing on the involvement of β-catenin localization. Analyzing the transcriptome data and benefiting from the molecular classification tool, we undertook an in-depth analysis of muscle-invasive bladder cancers to uncover the molecular characteristics of the neuroendocrine-like differentiation. The study explored the contribution of transcription factors and chromatin remodeling complexes to neuroendocrine differentiation in bladder cancer. The study revealed a significant correlation between β-catenin localization and neuroendocrine differentiation in muscle-invasive bladder tumors, highlighting the molecular complexity of neuroendocrine-like tumors. Enrichment of YY1 transcription factor, E2F family members, and Polycomb repressive complex components in β-catenin-positive tumors suggest their potential contribution to neuroendocrine phenotypes. Our findings contribute valuable insights into the molecular complexity of neuroendocrine-like bladder tumors. By identifying potential therapeutic targets and refining diagnostic strategies, this study advances our understanding of endocrinology in the context of bladder cancer. Further investigations into the functional implications of these molecular relationships are warranted to enhance our knowledge and guide future therapeutic interventions.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"115 9","pages":"2985-2997"},"PeriodicalIF":4.5,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.16275","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141617467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Estimation of self-funded human papillomavirus vaccine recipients from Japan's previously assumed “unvaccinated generation”","authors":"Mariya Kobayashi,&nbsp;Satoshi Nakagawa,&nbsp;Yutaka Ueda,&nbsp;Asami Yagi,&nbsp;Mamoru Kakuda,&nbsp;Kosuke Hiramatsu,&nbsp;Tadashi Kimura","doi":"10.1111/cas.16272","DOIUrl":"10.1111/cas.16272","url":null,"abstract":"<p>Precise vaccination data is essential to accurately estimate the effectiveness of the human papillomavirus (HPV) vaccine against HPV-related cancers. In Japan, the number of subsidized HPV vaccinations can be tracked through registries, but the number of self-funded vaccinations has not been tracked. The number of individuals who chose to receive the vaccine at their own expense, despite being ineligible for public subsidies due to their age, is unknown and has been nominally considered to be zero. Our aim is to produce a more accurate estimate of this number using recently released proprietary data. First, we estimated the total number of self-funded HPV vaccinations occurring from 2010 to 2012 using public data from the Ministry of Health, Labour and Welfare and our previously reported data on the number of HPV vaccinations eligible for public subsidy. Second, using proprietary data from the vaccine manufacturer, we calculated the distribution of self-funded vaccination shots by age. Finally, we combined these data to estimate the number of self-funded HPV vaccinations by birth fiscal year (FY) relative to a yearly reference population. We found that 78,264 individuals born in FY1993 and 58,190 born in FY1992 self-funded their vaccinations, representing 13.6% and 10.0% of the reference population, respectively. Additionally, we found that 5%–10% of individuals born from FY1986 to FY1991 self-funded their vaccinations. Our study revealed for the first time that a certain number of individuals from the “HPV unvaccinated generation,” ineligible for subsidies due to age restrictions, chose to self-fund their vaccinations.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"115 9","pages":"3099-3106"},"PeriodicalIF":4.5,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.16272","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141591808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"When and how should next-generation sequencing and comprehensive genomic profiling assays be performed?","authors":"Tadashi Nishimura,&nbsp;Takumi Fujiwara,&nbsp;Hajime Fujimoto","doi":"10.1111/cas.16270","DOIUrl":"10.1111/cas.16270","url":null,"abstract":"&lt;p&gt;I have worked as a respiratory physician in a community hospital for 8 years. During that time, lung cancer treatment has undergone a major paradigm shift. Targeted therapy for lung cancer has expanded, and most patients with non-small cell lung cancer (NSCLC) are now being evaluated using genetic analysis with a next-generation sequencing or a multiplex reverse transcriptase polymerase chain reaction assay. Ishida et al. provide an excellent study that explains the utility of comprehensive genomic profiling assays.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; However, the hospital where I work is a community hospital and access to these tests is limited. I was inspired by this study and would like to share two clinical questions regarding current companion diagnostics. And if possible, I would like to hear an experts opinion on genomic medicine.&lt;/p&gt;&lt;p&gt;First, is it possible to measure all genes with only one next-generation sequencing test? In the case of epidermal growth factor receptor (EGFR), discrepancies between next-generation sequencing and PCR have been reported.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; In Sakaguchi et al., EGFR-tyrosine kinase inhibitors were reported to be successful even in cases reported as negative by next-generation sequencing and positive for EGFR by PCR. For the ALK fusion gene, 15.5% of immunohistochemistry-positive patients are negative for next-generation sequencing tests.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; Therefore, the usefulness of immunohistochemistry in detecting ALK-positive patients has also attracted attention. Next-generation sequencing is also useful for measuring the resistance mechanism of EGFR-positive lung cancer,&lt;span&gt;&lt;sup&gt;4, 5&lt;/sup&gt;&lt;/span&gt; and it might be important to use targeted therapy for sequencing in the future. Which test should a patient with lung cancer undergo first at diagnosis? Should each of these tests be performed separately or simultaneously? Adequate solutions to these problems have not yet been found.&lt;/p&gt;&lt;p&gt;The second question is whether there is a need for more than two tests using next-generation sequencing. The study by Ishida et al. is a high-impact paper discussing the usefulness of comprehensive genomic profiling assays.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; (In their paper, comprehensive genomic profiling assays refers to FoundationOne and the OncoGuide NCC Oncopanel System.) Their paper demonstrated that new targets were found in people who had already undergone a gene test and subsequently undergone comprehensive genomic profiling assays. Noteworthy in their paper are the details of the 20 individuals for whom new therapeutic targets were found. Was their first test a single-plex test or an Oncomine Dx Target Test Multi-CDx? What were the histological type, sex, and smoking history of theese 20 patients? These information will help us determine which patients should undergo comprehensive genomic profiling assays. As mentioned in their paper, Oncomine Dx Target Test Multi-CDx and comprehensive genomic profiling assays might","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"115 9","pages":"3194-3195"},"PeriodicalIF":4.5,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.16270","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141591812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Uveal melanoma distant metastasis prediction system: A retrospective observational study based on machine learning","authors":"Shi-Nan Wu,&nbsp;Dan-Yi Qin,&nbsp;Linfangzi Zhu,&nbsp;Shu-Jia Guo,&nbsp;Xiang Li,&nbsp;Cai-Hong Huang,&nbsp;Jiaoyue Hu,&nbsp;Zuguo Liu","doi":"10.1111/cas.16276","DOIUrl":"10.1111/cas.16276","url":null,"abstract":"<p>Uveal melanoma (UM) patients face a significant risk of distant metastasis, closely tied to a poor prognosis. Despite this, there is a dearth of research utilizing big data to predict UM distant metastasis. This study leveraged machine learning methods on the Surveillance, Epidemiology, and End Results (SEER) database to forecast the risk probability of distant metastasis. Therefore, the information on UM patients from the SEER database (2000–2020) was split into a 7:3 ratio training set and an internal test set based on distant metastasis presence. Univariate and multivariate logistic regression analyses assessed distant metastasis risk factors. Six machine learning methods constructed a predictive model post-feature variable selection. The model evaluation identified the multilayer perceptron (MLP) as optimal. Shapley additive explanations (SHAP) interpreted the chosen model. A web-based calculator personalized risk probabilities for UM patients. The results show that nine feature variables contributed to the machine learning model. The MLP model demonstrated superior predictive accuracy (Precision = 0.788; ROC AUC = 0.876; PR AUC = 0.788). Grade recode, age, primary site, time from diagnosis to treatment initiation, and total number of malignant tumors were identified as distant metastasis risk factors. Diagnostic method, laterality, rural–urban continuum code, and radiation recode emerged as protective factors. The developed web calculator utilizes the MLP model for personalized risk assessments. In conclusion, the MLP machine learning model emerges as the optimal tool for predicting distant metastasis in UM patients. This model facilitates personalized risk assessments, empowering early and tailored treatment strategies.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"115 9","pages":"3107-3126"},"PeriodicalIF":4.5,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.16276","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141591811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ACSL4 upregulates IFI44 and IFI44L expression and promotes the proliferation and invasiveness of head and neck squamous cell carcinoma cells","authors":"Darius Rupa,&nbsp;Hao-Wen Chuang,&nbsp;Chung-En Hu,&nbsp;Wen-Min Su,&nbsp;Shiou-Rong Wu,&nbsp;Herng-Sheng Lee,&nbsp;Ta-Chun Yuan","doi":"10.1111/cas.16236","DOIUrl":"10.1111/cas.16236","url":null,"abstract":"<p>Reprogramming of cellular energy metabolism, including deregulated lipid metabolism, is a hallmark of head and neck squamous cell carcinoma (HNSCC). However, the underlying molecular mechanisms remain unclear. Long-chain acyl-CoA synthetase 4 (ACSL4), which catalyzes fatty acids to form fatty acyl-CoAs, is critical for synthesizing phospholipids or triglycerides. Despite the differing roles of ACSL4 in cancers, our data showed that ACSL4 was highly expressed in HNSCC tissues, positively correlating with poor survival rates in patients. Knockdown of ACSL4 in HNSCC cells led to reduced cell proliferation and invasiveness. RNA sequencing analyses identified interferon-induced protein 44 (IFI44) and interferon-induced protein 44-like (IFI44L), encoded by two interferon-stimulated genes, as potential effectors of ACSL4. Silencing IFI44 or IFI44L expression in HNSCC cells decreased cell proliferation and invasiveness. Manipulating ACSL4 expression or activity modulated the expression levels of JAK1, tyrosine kinase 2 (TYK2), signal transducer and activator of transcription 1 (STAT1), interferon α (IFNα), IFNβ, and interferon regulatory factor 1 (IRF1), which regulate IFI44 and IFI44L expression. Knockdown of IRF1 reduced the expression of JAK1, TYK2, IFNα, IFNβ, IFI44, or IFI44L and diminished cell proliferation and invasiveness. Our results suggest that ACSL4 upregulates interferon signaling, enhancing IFI44 and IFI44L expression and promoting HNSCC cell proliferation and invasiveness. Thus, ACSL4 could serve as a novel therapeutic target for HNSCC.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"115 9","pages":"3026-3040"},"PeriodicalIF":4.5,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.16236","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141581294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolism score and machine learning models for the prediction of esophageal squamous cell carcinoma progression","authors":"Lu Chen,&nbsp;WenXin Zhang,&nbsp;Huanying Shi,&nbsp;Yongjun Zhu,&nbsp;Haifei Chen,&nbsp;Zimei Wu,&nbsp;Mingkang Zhong,&nbsp;Xiaojin Shi,&nbsp;Qunyi Li,&nbsp;Tianxiao Wang","doi":"10.1111/cas.16279","DOIUrl":"10.1111/cas.16279","url":null,"abstract":"<p>The incomplete prediction of prognosis in esophageal squamous cell carcinoma (ESCC) patients is attributed to various therapeutic interventions and complex prognostic factors. Consequently, there is a pressing demand for enhanced predictive biomarkers that can facilitate clinical management and treatment decisions. This study recruited 491 ESCC patients who underwent surgical treatment at Huashan Hospital, Fudan University. We incorporated 14 blood metabolic indicators and identified independent prognostic indicators for overall survival through univariate and multivariate analyses. Subsequently, a metabolism score formula was established based on the biochemical markers. We constructed a nomogram and machine learning models utilizing the metabolism score and clinically significant prognostic features, followed by an evaluation of their predictive accuracy and performance. We identified alkaline phosphatase, free fatty acids, homocysteine, lactate dehydrogenase, and triglycerides as independent prognostic indicators for ESCC. Subsequently, based on these five indicators, we established a metabolism score that serves as an independent prognostic factor in ESCC patients. By utilizing this metabolism score in conjunction with clinical features, a nomogram can precisely predict the prognosis of ESCC patients, achieving an area under the curve (AUC) of 0.89. The random forest (RF) model showed superior predictive ability (AUC = 0.90, accuracy = 86%, Matthews correlation coefficient = 0.55). Finally, we used an RF model with optimal performance to establish an online predictive tool. The metabolism score developed in this study serves as an independent prognostic indicator for ESCC patients.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"115 9","pages":"3127-3142"},"PeriodicalIF":4.5,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.16279","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141591809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multifaceted interactions between cancer cells and glial cells in brain metastasis","authors":"Kojiro Ishibashi,&nbsp;Eishu Hirata","doi":"10.1111/cas.16241","DOIUrl":"10.1111/cas.16241","url":null,"abstract":"<p>Cancer brain metastasis has a poor prognosis, is commonly observed in clinical practice, and the number of cases is increasing as overall cancer survival improves. However, experiments in mouse models have shown that brain metastasis itself is an inefficient process. One reason for this inefficiency is the brain microenvironment, which differs significantly from that of other organs, making it difficult for cancer cells to adapt. The brain microenvironment consists of unique resident cell types such as neurons, oligodendrocytes, astrocytes, and microglia. Accumulating evidence over the past decades suggests that the interactions between cancer cells and glial cells can positively or negatively influence the development of brain metastasis. Nevertheless, elucidating the complex interactions between cancer cells and glial cells remains challenging, in part due to the limitations of existing experimental models for glial cell culture. In this review, we first provide an overview of glial cell culture methods and then examine recent discoveries regarding the interactions between brain metastatic cancer cells and the surrounding glial cells, with a special focus on astrocytes and microglia. Finally, we discuss future perspectives for understanding the multifaceted interactions between cancer cells and glial cells for the treatment of metastatic brain tumors.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"115 9","pages":"2871-2878"},"PeriodicalIF":4.5,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.16241","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141591810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trastuzumab deruxtecan versus trastuzumab emtansine in Asian patients with HER2-positive metastatic breast cancer","authors":"Hiroji Iwata,&nbsp;Binghe Xu,&nbsp;Sung-Bae Kim,&nbsp;Wei-Pang Chung,&nbsp;Yeon Hee Park,&nbsp;Min Hwan Kim,&nbsp;Ling-Ming Tseng,&nbsp;Chi-Feng Chung,&nbsp;Chiun-Sheng Huang,&nbsp;Jee Hyun Kim,&nbsp;Joanne Wing Yan Chiu,&nbsp;Toshinari Yamashita,&nbsp;Wei Li,&nbsp;Anton Egorov,&nbsp;Soichiro Nishijima,&nbsp;Shunsuke Nakatani,&nbsp;Yuji Nishiyama,&nbsp;Masahiro Sugihara,&nbsp;Javier Cortés,&nbsp;Seock-Ah Im","doi":"10.1111/cas.16234","DOIUrl":"10.1111/cas.16234","url":null,"abstract":"<p>The global phase 3 DESTINY-Breast03 study (ClinicalTrials.gov; NCT03529110) showed statistically significant and clinically meaningful improvements in progression-free survival (PFS) and overall survival (OS) with trastuzumab deruxtecan (T-DXd) over trastuzumab emtansine (T-DM1) in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC) previously treated with trastuzumab and a taxane. Here, we report a subgroup analysis of Asian patients enrolled in DESTINY-Breast03. In total, 309 patients (149 in the T-DXd arm and 160 in the T-DM1 arm) from Asian countries and regions were randomized. At data cutoff (July 25, 2022), the median duration of follow-up in the Asian subpopulation was 29.0 months with T-DXd and 26.0 months with T-DM1. The PFS (determined by blinded independent central review) hazard ratio was 0.30 (95% confidence interval 0.22–0.41) favoring T-DXd over T-DM1 (median PFS 25.1 vs. 5.4 months). Median OS was not reached in the T-DXd arm and was 37.7 months in the T-DM1 arm. The median treatment duration was 15.4 months with T-DXd and 5.5 months with T-DM1. The incidence of grade ≥3 drug-related treatment-emergent adverse events was similar between both treatment arms (49.0% vs. 46.5%) and was consistent with the overall DESTINY-Breast03 population. Adjudicated drug-related interstitial lung disease or pneumonitis occurred in 12.9% of patients treated with T-DXd and 2.5% treated with T-DM1, with a higher incidence in Japanese patients; none of these were grade ≥4 events. These efficacy and safety data reinforce the favorable benefit–risk profile of T-DXd in HER2-positive mBC, including in the Asian subgroup.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"115 9","pages":"3079-3088"},"PeriodicalIF":4.5,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.16234","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141560124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}