Cancer reports最新文献

{"title":"Homozygous FANCM Variant c.5101C>T p.(Gln1701*) in a Patient With Early Onset Breast Cancer, Chemotherapy Toxicity, and Chromosome Fragility: A Case Report","authors":"Sonja Sulkava,&nbsp;Anna H. Hakonen,&nbsp;Rikke Christensen,&nbsp;Minna Pöyhönen,&nbsp;Heli Nevanlinna","doi":"10.1002/cnr2.70283","DOIUrl":"https://doi.org/10.1002/cnr2.70283","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Biallelic <i>FANCM</i> variants are linked to a Fanconi anemia-like cancer predisposition syndrome, which includes early onset breast cancer, chemotherapy toxicity, and chromosome fragility. Additionally, heterozygous truncating variants have been linked to increased breast cancer risk. However, the published results have been inconsistent, and the risks and the functional effects associated with the variants also vary depending on the position in the gene, with N-terminal truncating variants having a stronger effect. Compared to other <i>FANCM</i> variants studied, milder patient phenotypes and only late onset breast cancer have been reported for the homozygous C-terminal c.5101C&gt;T variant, which is enriched in Finland.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Case</h3>\u0000 \u0000 <p>We report here a Finnish patient, homozygous for the <i>FANCM</i> c.5101C&gt;T p.(Gln1701*) variant, who manifested with early onset triple-negative breast cancer, chemotherapy toxicity, and chromosome fragility. Homozygosity for c.5101C&gt;T has previously been reported in two Finnish siblings with primary ovarian insufficiency and chromosome fragility.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings suggest that the C-terminal <i>FANCM</i> variant c. 5101C&gt;T may also be linked to a phenotype similar to the phenotype associated with N-terminal truncating variants when inherited in a homozygous state.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"8 8","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cnr2.70283","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144869966","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":"Global Burden and Gender Disparities in Head and Neck Cancers Among Adults Aged 40–64, 1990–2021: A Systematic Analysis From the Global Burden of Disease Study 2021","authors":"Zhuoding Luo,&nbsp;Yihan Huang,&nbsp;Renjing Ye,&nbsp;Min Yin","doi":"10.1002/cnr2.70287","DOIUrl":"https://doi.org/10.1002/cnr2.70287","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Head and neck cancer (HNC) is a significant global health concern, with incidence rising after the age of 40. This study aims to analyze the trends in prevalence, incidence, mortality, and disability-adjusted life years (DALYs), focusing on regional and gender differences.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This research utilized data from the Global Burden of Disease (GBD) 2021 study. Key metrics such as the age-standardized prevalence rate (ASPR), age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), and age-standardized disability-adjusted life years rate (ASDR) were analyzed. These metrics were used to examine trends from 1990 to 2021, focusing on gender and regional differences, and projections were made using the Nordpred method to predict future disease burdens up to 2045. The analysis covered 204 countries and regions and focused on cancers of the lip and oral cavity, nasopharynx, other pharynx, and larynx.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>From 1990 to 2021, the prevalence of HNC in the 40–64 age group nearly doubled, yet the ASPR remained stable. In contrast, ASIR, ASMR, and ASDR showed a decreasing trend. The analysis revealed significant gender differences, with males generally exhibiting higher ASIR, ASMR, and ASDR than females. However, the prevalence and incidence rates among females showed a faster increase in certain regions, particularly in lower SDI countries.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The study concludes that while the overall burden of HNC has shifted with a stable ASPR and decreasing ASIR, ASMR, and ASDR, gender-specific and region-specific strategies are essential to effectively address the risk factors associated with HNC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"8 8","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cnr2.70287","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144870027","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":"Chemotherapy-Induced Peripheral Polyneuropathy in Pediatric Acute Lymphoblastic Leukemia: A Case Report on Manifestation, Management, and Outcome","authors":"Eman Al Mattar,&nbsp;Sondus Al Sharidah,&nbsp;Omnia A. Hashem","doi":"10.1002/cnr2.70293","DOIUrl":"https://doi.org/10.1002/cnr2.70293","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Chemotherapy-induced peripheral polyneuropathy (CIPN) is a debilitating side effect of cancer treatment such as in acute lymphoblastic leukemia (ALL). Characterized by the dysfunction of the peripheral nervous system, CIPN can occur in 90% of pediatric patients, significantly impairing their quality of life. In most cases, it necessitates the modification of standard chemotherapy regimens, which can compromise the treatment efficacy and increase the risk of relapse.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Case</h3>\u0000 \u0000 <p>We report a 16-year-old boy with ALL who developed CIPN during induction therapy. A multidisciplinary, individualized treatment approach combined with regular follow-ups ensured optimal management. The patient achieved complete remission with significant improvement in mobility and neurological functions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Early recognition and comprehensive management of CIPN in pediatric ALL patients are essential to optimizing outcomes while maintaining the overall efficacy of chemotherapy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"8 8","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cnr2.70293","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144870025","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":"Long-Term Survival Obtained by Repeated Cytoreductive Surgery and S-1 Plus Cisplatin Chemotherapy at Each Instance of Disease Progression in a Patient With Metastatic Urachal Carcinoma: A Case Report","authors":"Masayasu Urushibara,&nbsp;Daisuke Kato,&nbsp;Taisuke Okumura,&nbsp;Akihiro Kojima,&nbsp;Yuichiro Kato,&nbsp;Takeshi Shirakawa,&nbsp;Yohei Shimizu,&nbsp;Tsunehiro Nenohi,&nbsp;Yuki Matsumoto,&nbsp;Noriyuki Matsutani,&nbsp;Tatsuya Aso,&nbsp;Mikiko Takahashi,&nbsp;Kazuhiro Ishizaka,&nbsp;Minato Yokoyama","doi":"10.1002/cnr2.70317","DOIUrl":"https://doi.org/10.1002/cnr2.70317","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Urachal carcinoma (URC) is a rare tumor of the urinary bladder, of which the histology usually resembles that of colorectal adenocarcinoma. Achievement of cure in patients with metastatic URC is difficult, and the survival rate of these patients has remained unsatisfactory despite various efforts.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Case</h3>\u0000 \u0000 <p>A 74-year-old female patient presented to us complaining of gross hematuria. Abdominal and thoracic computed tomography revealed a mass in the dome of the bladder with a single lung nodule. The two tumors, which were resected by partial cystectomy and video-assisted thoracic surgery, respectively, were diagnosed by postoperative histopathology as adenocarcinomas. Subsequent to the surgeries, bilateral ovarian metastases and another lung metastasis, which appeared metachronously, were also resected. The repeated cytoreductive surgery combined with administration of S-1 plus cisplatin chemotherapy at each instance of disease progression eventually yielded a durable progression-free survival; even at 5 years after the initial therapy, the patient remained asymptomatic with no limitation of activities despite the failure to achieve “cure”.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Not only some degree of sensitivity of the tumor to chemotherapy, but also the repeated cytoreductive surgeries might allow prolonged survival with a good quality of life in elderly patients with metastatic URC, even in the absence of cure and failure of genetic testing to suggest any potentially effective second-line drugs. To improve the survival of patients with metastatic URC, complementary therapy suggested by the results of genomic profiling may be necessary along with other multimodality therapy, including sequential metastasectomy and chemotherapy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"8 8","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cnr2.70317","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144869221","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":"Complete Response to Nivolumab and Ipilimumab After Pazopanib Discontinuation in a Seven-Year-Old Girl With Alveolar Soft Part Sarcoma: A Case Report and Literature Review","authors":"Aziz Eghbali,&nbsp;Mobin Obeidinia,&nbsp;Hamideh Sadat Mirmohammadi,&nbsp;Roghayeh Rahimiafazal,&nbsp;Arya Shirani","doi":"10.1002/cnr2.70305","DOIUrl":"https://doi.org/10.1002/cnr2.70305","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Alveolar soft part sarcoma (ASPS) is an extremely rare neoplasm that often presents with metastatic disease at diagnosis, leading to a poor prognosis. Conventional chemotherapy is generally ineffective against ASPS. Recent studies, nonetheless, suggest that tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) may be effective treatment options.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Case</h3>\u0000 \u0000 <p>We present a seven-year-old girl with stage IV ASPS in whom initial therapy with pazopanib, a TKI, had resulted in significant gastrointestinal side effects and poor drug compliance. We switched her treatment to an ICI regimen, a combination of nivolumab and ipilimumab, which led to a complete response.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This case highlights the value of ICIs as potential treatment options for ASPS in the pediatric population, especially in patients who cannot tolerate TKIs' side effects.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"8 8","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cnr2.70305","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144853822","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":"Integrative Genomic and Functional Approaches Identify FUOM as a Key Driver and Therapeutic Target in Cervical Cancer","authors":"Wenzhi Jiao,&nbsp;Shanshan Liu,&nbsp;Jianwei Shi,&nbsp;Minmin Yu","doi":"10.1002/cnr2.70306","DOIUrl":"https://doi.org/10.1002/cnr2.70306","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cervical cancer remains a global public health challenge, particularly in regions with limited access to screening and vaccination. While high-risk HPV infection is the primary cause, the genetic and molecular mechanisms driving cervical cancer progression are not fully understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study integrates Mendelian randomization (MR) and single-cell RNA sequencing (scRNA-seq) to identify causal eQTL-related genes and explore their roles in tumorigenesis. Functional experiments were conducted to validate key findings.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>MR analysis identified eQTL-related genes with significant causal associations with cervical cancer. Functional enrichment and Gene Set Variation Analysis (GSVA) revealed their involvement in key pathways. scRNA-seq explored cell-specific expression patterns and immune cell infiltration in the tumor microenvironment (TME). In vitro experiments, including qRT-PCR, siRNA knockdown, migration, proliferation, and colony formation assays, validated the biological roles of pivotal genes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 307 eQTL-related genes were identified, enriched in pathways such as Th17 cell differentiation, TNF, and IL-17 signaling. scRNA-seq revealed cell-specific expression of key genes, including FUOM, which was elevated in cervical cancer cells. FUOM knockdown significantly reduced cell proliferation (by 37%, <i>p</i> &lt; 0.001), migration (by 43%, <i>p</i> &lt; 0.001), and colony formation (by 62%, <i>p</i> &lt; 0.001). Regulatory analysis identified miRNAs as upstream modulators of these genes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study identifies FUOM as a novel driver gene in cervical cancer progression and highlights its role in tumorigenesis and immune modulation. These findings provide insights into potential biomarkers and therapeutic targets, offering a foundation for personalized treatment strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"8 8","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cnr2.70306","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144853859","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":"Bioinformatics Analysis Identifies Lipid Droplet-Associated Gene Signatures as Promising Prognostic and Diagnostic Models for Endometrial Cancer","authors":"Vijayalakshmi N. Ayyagari,&nbsp;Miao Li,&nbsp;Paula Diaz-Sylvester,&nbsp;Kathleen Groesch,&nbsp;Teresa Wilson,&nbsp;Ejaz M. Shah,&nbsp;Laurent Brard","doi":"10.1002/cnr2.70313","DOIUrl":"https://doi.org/10.1002/cnr2.70313","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Effective diagnostic and prognostic tools are critical for early detection and improved outcomes in endometrial cancer (EC). Although metabolic dysregulation plays a key role in EC pathogenesis, the clinical relevance of lipid droplet–associated genes (LDAGs) remains largely unexplored. This study aims to establish LDAG-based gene signatures with strong diagnostic and prognostic potential in EC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To identify LDAG signatures with prognostic and diagnostic utility in EC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>A curated set of LDAGs was systematically analyzed across publicly available EC datasets to identify differentially expressed LDAGs (DE-LDAGs). Survival-associated DE-LDAGs were then identified using univariate Cox regression. A four-gene prognostic model was developed through LASSO-based feature selection followed by multivariate Cox regression and validated using Kaplan–Meier survival and time-dependent receiver operating characteristic (ROC) analyses. From the same pool of survival-associated DE-LDAGs, a six-gene diagnostic model was constructed using LASSO, ROC analysis, and logistic regression. Model performance was evaluated using ROC curves and support vector machine (SVM) classification. Functional enrichment and protein–protein interaction (PPI) network analyses were conducted to assess the biological relevance of the identified genes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <p>Our results demonstrate that the four-gene prognostic model (LMLN, LMO3, PRKAA2, and RAB10) stratified EC patients into high- and low-risk groups with significantly different survival outcomes (<i>p</i> &lt; 0.05; time-dependent AUC &gt; 0.70). The six-gene diagnostic model (AIFM2, ABCG1, LIPG, DGAT2, LPCAT1, and VCP) demonstrated near-perfect classification of tumor versus normal tissues (AUC ≈0.99 in ROC analysis; 99.8% accuracy in SVM analysis). Functional enrichment linked DE-LDAGs to lipid metabolism, ER stress response, cholesterol homeostasis, and autophagy, underscoring their biological relevance in EC pathobiology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study provides the first comprehensive analysis of LDAGs in EC, establishing robust prognostic and diagnostic gene signatures with strong biological relevance. These signatures support a metabolism-driven framework for EC classification and may offer potential clinical utility in early detection, risk stratification, and personalized tr","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"8 8","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cnr2.70313","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144832380","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":"Real-World Response and Survival Outcomes and Treatment Patterns in Patients With Extensive Stage Small-Cell Lung Cancer Receiving Third-Line Treatment","authors":"Jair Bar,&nbsp;Qingqing Xu,&nbsp;Sudeep Karve,&nbsp;Pooja Hingorani,&nbsp;Amin A. Virani,&nbsp;Neal E. Ready","doi":"10.1002/cnr2.70289","DOIUrl":"https://doi.org/10.1002/cnr2.70289","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Patients with small-cell lung cancer (SCLC) primarily present with extensive stage (ES) disease and poor 5-year survival. There are few treatment options and limited data on outcomes in third-line (3L) ES SCLC to quantify unmet medical needs. This chart review evaluated real-world (RW) clinical outcomes and treatment patterns in these patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This retrospective study using electronic medical records included adult patients with ES SCLC (≥ 2 claims for metastasized lung cancer) who received ≥ 3 lines of therapy (LOT) at Cancer Treatment Centers of America (now City of Hope). Patients with other/multiple primary malignancies, non-SCLC histology, or treated through a clinical trial were excluded. Clinical outcomes included RW physician-reported response rates, duration of response (DOR), duration of clinical benefit (DoCB), overall survival (OS), and progression-free survival (PFS), stratified by platinum sensitivity and Eastern Cooperative Oncology Group performance status (ECOG-PS). Time-to-event outcomes were estimated via Kaplan–Meier. Treatment patterns were assessed, including the sequence of regimens by LOT and first-line (1L) platinum sensitivity status.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 113 eligible patients (median age 58 years), 54% were female, and 46% had a chemotherapy-free interval after 1L of &lt; 90 days. Tumor shrinkage, complete response, and stable disease were reported in 19%, 1%, and 13% of patients at 3L, respectively. The median DOR, DoCB, OS, and PFS were 2.8, 2.5, 5.8, and 2.4 months in 3L, respectively. Platinum-resistant versus sensitive patients in 1L had shorter time-to-event outcomes. Clinical outcomes were similar regardless of ECOG-PS status. Platinum-based chemotherapy rates decreased from 94% and 93% in 1L to 17% and 16% in 3L in platinum-sensitive and resistant patients, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These RW findings validate 3L results from clinical trials, demonstrating the limited clinical benefits with current therapies in 3L ES SCLC, and highlighting the urgent need for novel therapies that improve outcomes in this difficult-to-treat patient population.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"8 8","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cnr2.70289","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144815092","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":"Flavonoids as Promising Akt1 Inhibitors in Cancer Medicine: Insights From Molecular Docking, Dynamics, DFT Calculations, and In Vitro Validation","authors":"Shokoofeh Jamshidi,&nbsp;Ali Eghbalian,&nbsp;Setareh Shojaei,&nbsp;Amir Taherkhani,&nbsp;Mehran Feizi-Dehnayebi","doi":"10.1002/cnr2.70315","DOIUrl":"https://doi.org/10.1002/cnr2.70315","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The PI3K/Akt/mTOR signaling pathway is commonly deregulated in different types of cancers, contributing to tumor proliferation, persistence, and resistance to treatment. Akt1, a crucial kinase within this pathway, plays a critical role in tumor progression and the occurrence of therapeutic resistance. The emergence of resistance is a significant challenge in cancer therapy. Targeted therapies offer a promising method to overcome this challenge. Akt1 presents a promising target for therapeutic intervention.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Aims&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This study aimed to evaluate the binding affinities of 61 flavonoid-derived natural compounds to the Akt1 ATP-binding site using molecular docking with AutoDock to identify potential Akt1 inhibitors.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Cross-validation and Density Functional Theory analysis were conducted utilizing the SwissDock server and the Gaussian 09 W software suite for the top-ranked compounds. Following energy minimization, semi-flexible docking of flavonoids and the control inhibitor Ipatasertib was performed against the Akt1 ATP-binding pocket. Binding modes were analyzed using Discovery Studio Visualizer. Molecular dynamics simulations were conducted to assess the conformational stability and binding durability of the highest-scoring Akt1 inhibitor complex identified through molecular docking analyses. The pharmacokinetics and toxicity properties of the most potent Akt1 inhibitors were evaluated using the PreADMET tool. Also, the effect of the most potent Akt1 inhibitor on cell viability was studied in vitro through the 2,5-diphenyl-2H-tetrazolium bromide approach. Besides, the most promising compound was evaluated for its impact against the FOXO3 (an Akt1 downstream target) gene expression in MCF-7 cells.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Kaempferol 3-rutinoside-4′-glucoside and Kaempferol 3-rutinoside-7-sophoroside displayed exceptional binding affinities (Δ&lt;i&gt;G&lt;/i&gt;&lt;sub&gt;binding&lt;/sub&gt; = −21.79 and −20.73 kcal/mol; Ki = 106.03 aM and 640.24 aM), surpassing Ipatasertib (Δ&lt;i&gt;G&lt;/i&gt;&lt;sub&gt;binding&lt;/sub&gt; = −9.98 kcal/mol; Ki = 48.29 nM). Kaempferol 3-rutinoside-4′-glucoside achieved a stable binding conformation within the Akt1 catalytic domain after 30 ns of molecular dynamics simulation. The compound Kaempferol 3-rutinoside-4′-glucoside was observed to suppress cell proliferation in MCF-7 cell lines. This effect was accompanied by an upregulation of FOXO3 expression, suggesting a connection to the induction of the apoptosis pathway.&lt;/p&gt;\u0000 ","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"8 8","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cnr2.70315","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144832851","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":"Interventional Treatment Is an Effective Approach to Relieve Symptoms in Patients With Malignant Tracheoesophageal Fistula","authors":"Pei Huang,&nbsp;Jinghua Cui,&nbsp;Zhenbang Lie,&nbsp;Jing Li","doi":"10.1002/cnr2.70312","DOIUrl":"https://doi.org/10.1002/cnr2.70312","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>A malignant tracheoesophageal fistula (mTEF) is a complication of primary tumor growth or the recurrence of esophageal tumors or lung carcinoma. Patients with mTEF have lower survival and quality of life than those who do not develop this complication. Esophageal cancer (EC), a common gastrointestinal malignancy, ranks among the world's leading causes of cancer-related death. The low survival rate in patients with EC is attributed to malnutrition, repeated aspiration, and severe infection; the mean survival duration is 2–4 months after diagnosis. This study investigated the clinical characteristics of patients with EC complicated with mTEF and the efficacy of various treatment regimens.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study was a retrospective analysis of the clinical data of 51 patients with EC complicated with mTEF hospitalized at Guangdong Provincial People's Hospital from February 2007 to May 2021. Patients were divided into three groups according to their treatment regimen: a traditional medical (TM) treatment group, an esophageal intervention (EI) treatment group, and an airway intervention (AI) treatment group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of the 51 patients, 22 received TM treatment, 13 received AI, and 16 received EI. The overall median survival duration was 87 days (TM group, 42 days; AI group, 108 days; EI group, 104 days) and the overall mean survival duration was 130.1 days (TM group, 88.1 days; AI group, 153.5 days; EI group, 166.1 days). Cox regression analysis revealed that the treatment regimen was an independent predictive risk factor for increased survival 1 month after treatment in patients with EC complicated with mTEF, and most symptoms were relieved in the EI and AI groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Interventional treatment of the esophagus and airway in patients with EC complicated with mTEF is an effective approach to improve symptoms and increase short-term survival.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"8 8","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cnr2.70312","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144811091","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}