Cancer Medicine最新文献

{"title":"Efficacy of the PanCareFollowUp eHealth Lifestyle Intervention for Survivors of Childhood, Adolescent and Young Adult Cancer","authors":"Selina R. van den Oever,&nbsp;Eline Bouwman,&nbsp;Helena J. H. van der Pal,&nbsp;Philippa C. Steensma,&nbsp;Vera Araujo-Soares,&nbsp;Morven Brown,&nbsp;Tomas Kepak,&nbsp;Katerina Kepakova,&nbsp;Marta Fiocco,&nbsp;Lucy M. M. Fremouw,&nbsp;Maria M. W. Koopman,&nbsp;Raphaële R. L. van Litsenburg,&nbsp;Patrick van der Torre,&nbsp;Joyce Wilbers,&nbsp;Roderick Skinner,&nbsp;Leontien C. M. Kremer,&nbsp;Jacqueline Loonen,&nbsp;Saskia M. F. Pluijm,&nbsp;the PanCareFollowUp consortium","doi":"10.1002/cam4.70694","DOIUrl":"https://doi.org/10.1002/cam4.70694","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>A healthy lifestyle may prevent or mitigate late effects in childhood, adolescent and young adult (CAYA) cancer survivors. To support survivors in adopting healthier behaviours, the PanCareFollowUp (PCFU) Lifestyle intervention was developed, encompassing 4 months of online lifestyle coaching aimed at achieving a personal lifestyle goal. The aims of this study were to (1) determine the efficacy of this intervention on lifestyle outcomes over time and (2) identify predictors for goal achievement.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Patients and Methods</h3>\u0000 \u0000 <p>Fifty-eight survivors were enrolled. Outcomes were assessed at baseline (T0), after 4 months of coaching (T1) and after 4 months of follow-up (T2). The primary outcome included the percentage of survivors successful in achieving and sustaining their goal, whereas secondary outcomes included differences in body mass index (BMI), diet and physical activity. To evaluate the adjusted, longitudinal effects on secondary outcomes, linear mixed models were estimated. Predictors for goal achievement were identified through logistic regression analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>At T1 and T2, 68% and 76% of goals were achieved or sustained, respectively. Mean differences between T2 and T0 showed significant improvements in BMI (−0.5 kg/m²), diet (−0.6 points) and physical activity (+7.7 h/week). Estimation of multivariable models also showed positive effects. Participants with a lower BMI and fewer depressive feelings at baseline were more likely to achieve and/or sustain their goals at T2.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Findings suggest that the PCFU Lifestyle intervention supports survivors in making lifestyle changes. Results can be used to inform a subsequent randomised intervention study and integrate lifestyle coaching into care.</p>\u0000 \u0000 <p><b>Trial Registration:</b> International Clinical Trial Registry Platform (ICTRP) number: NL8932 (ICTRP Search Portal [who. int]). Registered on 29 September 2020</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 5","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70694","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143513543","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":"Interventions to Support Transitions in Care Among Patients With Cancer: A Scoping Review","authors":"Negar Rezaei,&nbsp;Jaling Kersen,&nbsp;Abigail Thomas,&nbsp;Stefan Kurbatfinski,&nbsp;Diane Lorenzetti,&nbsp;Khara Marissa Sauro","doi":"10.1002/cam4.70660","DOIUrl":"https://doi.org/10.1002/cam4.70660","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The cancer journey from diagnosis through survivorship is complex and involves care from many healthcare providers across a variety of settings. Navigating the transitions between care providers and settings can be improved through interventions. The objective of this study was to map and characterize evidence on interventions to improve transitions in care among patients with cancer.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>Six databases were searched to identify relevant studies that described or evaluated interventions to support transitions in care for patients with cancer. Data on the interventions, the type of transition in care, type of cancer, and outcomes (including measure of effectiveness) were abstracted. Data were synthesized and analyzed using descriptive statistics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Result</h3>\u0000 \u0000 <p>Of the 38,876 data sources identified, 150 were included. Most included studies were from the United States and were observational studies exploring interventions to facilitate the transition from treatment to survivorship (followed by interventions for the transition from hospital to home) among patients with breast cancer (followed by gastrointestinal cancers, lung cancers, and hematologic cancers). Interventions that were found to be effective were most commonly those that facilitated the transition from diagnosis to treatment and for the transition from hospital to home.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This comprehensive synthesis is an important resource for those trying to improve transitions in care for patients living with and beyond cancer. Despite the large body of evidence identified, gaps remain; there is a paucity of studies exploring transitions in care during cancer treatment and among some cancers (e.g., brain tumors, head and neck, pancreatic).</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 5","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70660","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143513545","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":"National Survey of Real-World Australian Treatment Patterns for Patients With Very-Early-To Intermediate-Stage Hepatocellular Carcinoma","authors":"Stuart K. Roberts,&nbsp;Ammar Majeed,&nbsp;Kiran Rasaratnam,&nbsp;John K. Olynyk,&nbsp;Nicholas Shackel,&nbsp;Marnie Wood,&nbsp;Simone I. Strasser,&nbsp;Alan Wigg","doi":"10.1002/cam4.70722","DOIUrl":"https://doi.org/10.1002/cam4.70722","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background/Purpose of the Study</h3>\u0000 \u0000 <p>The treatment landscape for very early to intermediate stage hepatocellular carcinoma (HCC) is rapidly evolving, with new data and treatments emerging in recent years. There is a lack of data on current patterns of management for very early to intermediate stage HCC in Australian clinical practice and the role of newly emerging treatment options.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Multidisciplinary specialists involved in HCC management (<i>N</i> = 86) participated in one of six state-based meetings across Australia. Specialists were surveyed on their preferred management approaches at key clinical decision points for four patient case studies ranging from very early to intermediate stage HCC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Preferred management strategies for each of the patient case studies were largely consistent with current Australian HCC recommendations in relation to surveillance, diagnosis, and treatment of HCC although the preferred initial treatment selection varied considerably within and between hepatologists and other craft groups. There was, however, growing interest in emerging treatments, including stereotactic ablative body radiotherapy (SABR) for early stage HCC and systemic treatments used as adjuvant therapy or in combination with locoregional therapy in early and intermediate-stage HCC. However, many participants required more data on these treatment modalities before incorporating them into routine clinical practice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The heterogeneity of (very) early to intermediate-stage HCC patients and the increasing number of available treatment options means clinical decision-making, including treatment selection, is becoming more complex and diverse. More data are required to define the role of SABR and systemic therapies in very early to intermediate stage HCC before being adopted as standard of care in Australia.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 5","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70722","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143513544","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":"Data-Driven Molecular Typing: A New Frontier in Esophageal Cancer Management","authors":"Yue Du,&nbsp;Bianli Gu,&nbsp;Linlin Shi,&nbsp;Yong She,&nbsp;Qi Zhao,&nbsp;Shegan Gao","doi":"10.1002/cam4.70730","DOIUrl":"https://doi.org/10.1002/cam4.70730","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Esophageal squamous cell carcinoma (ESCC) is a predominant and highly lethal form of esophageal cancer, with a five-year survival rate below 20%. Despite advancements, most patients are diagnosed at advanced stages, limiting effective treatment options. Multi-omics integration, encompassing somatic genomic alterations, inherited genetic mutations, transcriptomics, proteomics, metabolomics, and single-cell sequencing, has enabled the identification of distinct molecular subtypes of ESCC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>This article systematically reviewed the current status of molecular subtyping of ESCC based on big data, summarized unique subtypes with differing treatment responses and prognostic outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Result</h3>\u0000 \u0000 <p>Key findings included subtype-specific genetic mutations, signaling pathway alterations, and metabolomic profiles, which offer novel biomarkers and therapeutic targets. Furthermore, this review discusses the link between molecular subtypes and immunotherapy efficacy, chemotherapy response, and drug development.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These insights highlight the potential of omics-based molecular typing to transform ESCC management and facilitate personalized treatment strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 5","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70730","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143513633","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":"Durvalumab Monotherapy in Complex Advanced Hepatocellular Carcinoma: A Real-World Study of Patients Ineligible for Combination Immunotherapy","authors":"Chihiro Miwa,&nbsp;Sadahisa Ogasawara,&nbsp;Takuya Yonemoto,&nbsp;Sae Yumita,&nbsp;Tomomi Okubo,&nbsp;Miyuki Nakagawa,&nbsp;Keisuke Koroki,&nbsp;Masanori Inoue,&nbsp;Naoya Kanogawa,&nbsp;Masato Nakamura,&nbsp;Takayuki Kondo,&nbsp;Shingo Nakamoto,&nbsp;Norio Itokawa,&nbsp;Masanori Atsukawa,&nbsp;Ei Itobayashi,&nbsp;Naoya Kato","doi":"10.1002/cam4.70642","DOIUrl":"https://doi.org/10.1002/cam4.70642","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Combination immunotherapy is the standard of care for advanced hepatocellular carcinoma (HCC). However, some patients are unsuitable for such treatment. This study investigated the safety and effectiveness of durvalumab monotherapy in a real-world cohort with advanced HCC who were poor candidates for combination immunotherapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We retrospectively analyzed data from 35 patients with advanced HCC treated with durvalumab monotherapy across three Japanese institutions between January and December 2023. Patients were selected based on their ineligibility for combination immunotherapy or vascular endothelial growth factor inhibiting tyrosine kinase inhibitors (VEGF-TKIs). Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs) were assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The median age was 71 years, with 51.4% classified as Child–Pugh B or C. Notably, 91.4% of patients were ineligible for the IMbrave150 or HIMALAYA trials. Median PFS was 2.7 months (95% CI: 1.84–6.2) and the median OS was not reached. The ORR and DCR were 2.9% and 51.4%, respectively. Grade ≥ 3 treatment-related AEs (trAEs) occurred in 8.6% of patients, with a discontinuation rate of 11.4% due to AEs. The most common AEs were aspartate aminotransferase (AST) increased (34.3%), hypoalbuminemia (28.6%), and alanine aminotransferase (ALT) increased (25.7%). Immune-mediated AEs (imAEs) affected 14.3% of the patients. The albumin-bilirubin (ALBI) scores showed no significant deterioration in patients without progressive disease (PD) over 12 weeks after treatment initiation (<i>p</i> = 0.771).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Durvalumab monotherapy demonstrated a favorable safety profile and comparable effectiveness to VEGF-TKIs in patients with advanced HCC unsuitable for combination immunotherapy, especially for those with Child–Pugh B status.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 5","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70642","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497054","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":"Feature Selection and Network-Driven Analyses to Unveil Common RNA Signatures in Colon and Pancreatic KRAS-Mutant Cancers","authors":"Katia Pane,&nbsp;Mario Zanfardino,&nbsp;Anna Maria Grimaldi,&nbsp;Ilaria Leone,&nbsp;Silvia Nuzzo,&nbsp;Marco Salvatore,&nbsp;Monica Franzese","doi":"10.1002/cam4.70468","DOIUrl":"https://doi.org/10.1002/cam4.70468","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Colon cancer and pancreatic ductal adenocarcinoma are among the most aggressive tumors for which therapeutic options are limited. Both cancers share common features, such as some KRAS pathogenic variants and common epidemiology. The integration of multidimensional datasets by combining machine learning and bioinformatics approaches could provide deeper insights into the intricate KRAS-related networks underlying cancer progression and unveil novel biomarkers and potential therapeutic targets. This study aimed to uncover colon and pancreatic cancers that shared transcriptional changes closely related to KRAS missense mutations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Feature Selection (FS) technique and Qiagen's Ingenuity Pathway Analysis (IPA) were used to combine DNA-Seq and RNA-Seq data from mutant and wild-type (WT) KRAS colon and pancreatic tumor samples.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>From the FS, we prioritized 70 genes (54 protein-coding genes and 16 ncRNA-coding genes) that were able to discriminate between WT and mutated KRAS patients. These genes were involved in KRAS signaling and other related processes, such as EMT signaling, glycolysis, apical junction, Wnt/beta-catenin signaling, and IL-2/STAT5 signaling. Using IPA, we identified a top-scoring network of 19 upregulated genes in both tumor types stratified into mutant KRAS and WT KRAS samples. For a set of genes, qRT–PCR performed on colon and pancreatic representative cancer cell lines showed concordant expression trends when comparing colon-dominant KRAS mutants versus WT KRAS and dominant pancreatic KRAS mutants versus WT KRAS, as expected according to in silico analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings may provide insight into the common transcriptional signatures potentially underlying colon and pancreatic KRAS-mutant cancers. However, further studies are needed to elucidate the diagnostic and prognostic value of targets identified as common features in our study.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 5","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70468","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497056","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":"The Prognostic Value of Tumor-Associated Neutrophils in Colorectal Cancer: A Systematic Review and Meta-Analysis","authors":"Mengyuan Jiang,&nbsp;Rui Zhang,&nbsp;Min Huang,&nbsp;Jing Yang,&nbsp;Qianqian Liu,&nbsp;Ziru Zhao,&nbsp;Ya Ma,&nbsp;Hongfan Zhao,&nbsp;Min Zhang","doi":"10.1002/cam4.70614","DOIUrl":"https://doi.org/10.1002/cam4.70614","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Tumor-associated neutrophils (TANs) are important components of the colorectal cancer (CRC) microenvironment. However, their role in CRC remains controversial. This study aimed to assess the prognostic value of TANs in patients with CRC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We searched the PubMed, EMBASE, and Cochrane Library databases for eligible studies published until January 9, 2023. The pooled hazard ratios (HRs) and odds ratios (ORs) with their 95% confidence intervals (95% CI) were calculated with a random-effects model to assess survival outcomes and clinicopathological features. Subgroup analyses were further conducted to identify potential sources of heterogeneity. Funnel plots and Egger's test were used to measure publication bias.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 19 studies with 7721 patients were included in this meta-analysis. The pooled analysis indicated that high peritumoral TAN infiltration in CRC tissue was significantly associated with favorable cancer-specific survival (HR = 0.57; 95% CI: 0.38–0.86; <i>p</i> = 0.007), but not with overall survival or disease-free survival. No association between high intratumoral or unclear compartment TAN infiltration and CRC prognosis was found. Subgroup analyses showed that the association between TANs and the prognosis of CRC patients differed according to antibody types, tumor stage, quantitative methods, and follow-up time. High intratumoral TAN infiltration was significantly associated with histology type, whereas high TAN infiltration in an unclear compartment was significantly associated with gender, tumor location, and the primary tumor site.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>High TAN infiltration, especially in the peritumoral compartment, could be a potential prognostic marker in CRC. More high-quality studies are required to explore its specific prognostic value in CRC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 5","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70614","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497090","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":"A highly sensitive screening system to evaluate the reversibility of neuroendocrine prostate cancer to prostate adenocarcinoma","authors":"Tomohiro Fukui,&nbsp;Kosuke Okasho,&nbsp;Yukiko Okuno,&nbsp;Maki Fujiwara,&nbsp;Kensuke Hikami,&nbsp;Arinobu Fukunaga,&nbsp;Takuro Sunada,&nbsp;Yuki Kita,&nbsp;Takayuki Sumiyoshi,&nbsp;Takayuki Goto,&nbsp;Ryoichi Saito,&nbsp;Osamu Ogawa,&nbsp;Takashi Kobayashi,&nbsp;Shusuke Akamatsu","doi":"10.1002/cam4.70047","DOIUrl":"https://doi.org/10.1002/cam4.70047","url":null,"abstract":"&lt;p&gt;Prostate cancer grows in an androgen-dependent manner, and the standard therapy for advanced prostate cancer is endocrine therapy targeting the androgen receptor (AR) signaling pathway. However, with the widespread use of potent next-generation AR signaling inhibitors (ARSIs), the incidence of treatment-related neuroendocrine prostate cancer (t-NEPC), which is completely independent of the AR pathway, is rapidly rising.&lt;span&gt;&lt;sup&gt;1, 2&lt;/sup&gt;&lt;/span&gt; Unlike its AR-dependent ancestor, t-NEPC remains a poor prognosis cancer, lacking effective treatment options, and thus necessitating the exploration and development of innovative therapies.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Transdifferentiation of prostate adenocarcinoma into neuroendocrine prostate cancer (NEPC) occurs through lineage plasticity.&lt;span&gt;&lt;sup&gt;3-5&lt;/sup&gt;&lt;/span&gt; Lineage plasticity is a biological process that enhances cell survival by enabling adaptation to the environment, avoidance of stress, or tissue repair.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; Within cancer, lineage plasticity facilitates the development of therapy resistance in cancer cells by reprogramming into therapy-resistant phenotypes that bypass targeted therapies.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; This phenomenon is especially notable in cancer varieties where there are potent targeted therapies for key growth pathways, such as AR-driven prostate cancer, epidermal growth factor receptor (EGFR)-mutant lung cancer, and BRAF-mutant melanoma.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Recent genomic analyses have revealed several alterations enriched in t-NEPC, with the loss of tumor suppressor genes (&lt;i&gt;TP53&lt;/i&gt; and &lt;i&gt;RB1&lt;/i&gt;) being crucial genomic changes linked to t-NEPC.&lt;span&gt;&lt;sup&gt;3, 6&lt;/sup&gt;&lt;/span&gt; Moreover, epigenetic genes, such as &lt;i&gt;EZH2&lt;/i&gt; and &lt;i&gt;SOX2&lt;/i&gt;, induce neuroendocrine (NE) transdifferentiation.&lt;span&gt;&lt;sup&gt;7, 8&lt;/sup&gt;&lt;/span&gt; A study with gene-engineered mice lacking &lt;i&gt;Pten&lt;/i&gt; and &lt;i&gt;Rb1&lt;/i&gt;, or all three (&lt;i&gt;Pten&lt;/i&gt;, &lt;i&gt;Rb1&lt;/i&gt;, and &lt;i&gt;Trp53&lt;/i&gt;), showed reduced expression of AR and increased expression of NE-related genes, phenocopying human NEPC. Furthermore, using EZH2 inhibitors restored AR expression and sensitivity to antiandrogen therapy.&lt;span&gt;&lt;sup&gt;7&lt;/sup&gt;&lt;/span&gt; These findings suggest that plasticity in t-NEPC is potentially reversible, and regulating cellular lineage could serve as a novel therapeutic strategy. However, EZH2 inhibition did not increase AR expression or activity in organoids from human NEPC.&lt;span&gt;&lt;sup&gt;9&lt;/sup&gt;&lt;/span&gt; To date, the reversibility of lineage plasticity in prostate cancer has not been confirmed in human-derived t-NEPC clinical models.&lt;/p&gt;&lt;p&gt;One major hurdle in NEPC research is the paucity of human-derived t-NEPC cell lines suitable for genetic manipulation or large-scale compound screening. Previously, we created a novel t-NEPC cell line called KUCaP13, derived from a patient-derived xenograft (PDX) and verified its lineage originating from prostate adenocarcinoma.&lt;span&gt;&lt;sup&gt;10&lt;/sup&gt;&lt;/span&gt; The cell line's ","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 5","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70047","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497138","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":"circFOXK2 Stabilizes STMN1 mRNA via PABPC1 to Promote the Progression of NSCLC","authors":"Wei Chen,&nbsp;Weijun Zhao,&nbsp;Xianqiao Wu,&nbsp;Tianzheng Fang,&nbsp;Ziyuan Chen,&nbsp;Zixuan Chen,&nbsp;Wenmin Su,&nbsp;Xiaodong Zhao,&nbsp;Yuanyuan Hu,&nbsp;Yiping Xu,&nbsp;Shuai Fang,&nbsp;Chengwei Zhou","doi":"10.1002/cam4.70729","DOIUrl":"https://doi.org/10.1002/cam4.70729","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Lung cancer has a notably high incidence and mortality rate, and understanding its occurrence and development is crucial for effective treatment. Circular RNA is closely associated with tumor progression, playing a role in tumorigenesis and development by regulating gene expression and influencing cell proliferation and apoptosis. This study aims to explore the circFOXK2 role in NSCLC occurrence and development and to elucidate its underlying mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>qRT-PCR and Western Blot analyzed the expressions of circFOXK2, STMN1, and PABPCA in NSCLC cell lines, as well as their relationships. The roles of circFOXK2 and STMN1 in the proliferation, invasion, and migration of NSCLC cells were assessed through CCK8, EDU, and Transwell experiments. RNA pulldown assays with mass spectrometry elucidated the RNA-binding proteins of circFOXK2. Subcutaneous tumorigenesis and tail vein lung metastasis experiments analyzed the impact of circFOXK2 on tumor growth and metastasis in vivo.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In this study, we identified circFOXK2, which is significantly overexpressed in NSCLC, through bioinformatics screening. Elevated levels of circFOXK2 enhance the growth and metastasis of NSCLC cells. Furthermore, through experiments such as co-IP and mass spectrometry, we found that circFOXK2 interacts with PABPC1 to form a complex, which correlates positively with the progression and metastasis of tumors. Simultaneously, the circFOXK2/PABPC1 complex increases the stability of STMN1 mRNA, thereby promoting the transcription and translation of STMN1. Our experimental results indicate that the oncogenic effect of circFOXK2 requires the assistance of STMN1.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In summary, we have demonstrated the significant role of circFOXK2/PABPC1 in regulating STMN1 expression in NSCLC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 5","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70729","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497088","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":"CAR-T Cell Manufacturing for Hematological and Solid Tumors: From the Preclinical to Clinical Point of View","authors":"Sara Capolla,&nbsp;Maria Rasool,&nbsp;Giuseppe Toffoli,&nbsp;Michele Dal Bo","doi":"10.1002/cam4.70726","DOIUrl":"https://doi.org/10.1002/cam4.70726","url":null,"abstract":"<p>Cell therapy based on chimeric antigen receptor (CAR) T cells has represented a revolutionary new approach for treating tumors, especially hematological diseases. Complete remission rates (CRR) &gt; 80%–97% and 50%–90% overall response rates (ORR) have been achieved with a treatment based on CAR-T cells in patients with malignant B-cell tumors that have relapsed or are refractory to previous treatments. Toxicity remains the major problem. Most patients treated with CAR-T cells develop high-grade cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). However, the unprecedentedly high CRR and ORR have led to the approval of six CAR-T cell therapeutics by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA), prompting researchers to improve existing products and develop new ones. By now, around 1000 clinical trials based on CAR-T cells are registered at ClinicalTrials.gov: 82% are for hematological diseases, while the remaining 16% are for solid tumors. As a result of this increased research, an enormous amount of conflicting information has been accumulated in the literature, and each group follows its manufacturing protocols and performs specific in vitro testing. This review aimed to combine and compare clinical and preclinical information, highlighting the most used protocols to provide a comprehensive overview of the in vitro world of CAR-T cells, from manufacturing to their characterization. The focus is on all steps of the CAR-T cell manufacturing process, from the collection of patient or donor blood to the enrichment of T cells, their activation with anti-CD3/CD28 beads, interleukin-2 (IL-2) or IL-7 and IL-15 (induction of a more functional memory phenotype), and their transfection (viral or non-viral methods). Automation is crucial for ensuring a standardized final product.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 5","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70726","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497057","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}