Cancer treatment and research communications最新文献

{"title":"Effect of hypoxia on extracellular vesicles in malignant and non-malignant conditions","authors":"Vahid Niazi ,&nbsp;Soudeh Ghafouri-Fard","doi":"10.1016/j.ctarc.2025.100924","DOIUrl":"10.1016/j.ctarc.2025.100924","url":null,"abstract":"<div><div>Extracellular vesicles (EVs) are produced by virtually all types of cells and can be detected in nearly all extracellular places. These particles mediate intercellular communication and transfer their cargo to the recipient cells, inducing a variety of processes in these cells through transmission of several biomolecules such as miRNAs, lncRNAs, other transcripts and a variety of proteins. It has been documented that size, quantity, and expression of biomolecules in the EVs are influenced by the level of oxygen. In fact, hypoxia can affect several cellular processes through modulation of the cargo of these vesicles. Hypoxic exosomes derived from tumor cells have several protumoral effects on the recipient cells, including enhancement of proliferation, migration, and invasion in other tumoral cells, induction of metastasis in distant organs, stimulation of angiogenesis in the endothelial cells, and modulation of macrophage polarization. Hypoxic EVs also contribute to several non-malignant diseases. This review summarizes the effect of hypoxia on EVs cargo in malignant and nonmalignant diseases of different organs.</div></div>","PeriodicalId":9507,"journal":{"name":"Cancer treatment and research communications","volume":"43 ","pages":"Article 100924"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143799159","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":"At-home autologous hematopoietic cell transplant for adults with hematological malignancies. How frailty impacts and evolves during HCT procedure. An observational, longitudinal, and prospective study","authors":"Juan Ortiz ,&nbsp;María Teresa Solano ,&nbsp;Cristina Gallego ,&nbsp;Nuria Ballestar ,&nbsp;Noemi de Llobet ,&nbsp;Laia Guardia ,&nbsp;Raquel Salinas ,&nbsp;Alexandra Martínez-Roca ,&nbsp;Beatriz Merchán ,&nbsp;Paola Charry ,&nbsp;Joan Cid ,&nbsp;Miquel Lozano ,&nbsp;Enric Carreras ,&nbsp;Sara Laxe ,&nbsp;Concepción Closa ,&nbsp;María Suárez-Lledó ,&nbsp;Laura Rosiñol ,&nbsp;Carmen Martínez ,&nbsp;Montserrat Rovira ,&nbsp;Francesc Fernández-Avilés ,&nbsp;María Queralt Salas","doi":"10.1016/j.ctarc.2025.100920","DOIUrl":"10.1016/j.ctarc.2025.100920","url":null,"abstract":"<div><h3>Introduction and aims</h3><div>Since April 2021, the frailty state of patients is evaluated routinely in adults undergoing auto-HCT at our institution using the HCT Frailty Scale. The scale categorises each candidate as either fit, pre-fit or frail.</div></div><div><h3>Methods</h3><div>Our study includes 80 consecutive adults with lymphoprolipherative disorders (LPD) and multiple myeloma (MM) undergoing at-home auto-HCT at our institution between June 2021 and June 2023. An initial evaluation of frailty was conducted at first consultation (pre-apheresis), followed by a subsequent evaluation at day +100.</div></div><div><h3>Results</h3><div>The median age was 58 years (range: 19–69), 41 (51.2 %) patients were males, 45 (56.3 %) were diagnosed with MM and 35 with LPD. At the initial consultation, 24 (30.0 %) adults were classified as fit, 48 (60.0 %) as pre-frail, and 8 (10.0 %) as frail. Frail patients were more likely to be older (OR 1.16 <em>P</em> = 0.077), and to have a KPS &lt; 90 % (OR 27, <em>P</em> = 0.012), and also exhibit a higher number of comorbidities (HCT-CI&gt;3: OR 11.9, <em>p</em> = 0.035). However, the underlying diagnosis did not impact the incidence of frailty at the initial consultation (OR 0.99, <em>p</em> = 0.999).</div></div><div><h3>Conclusions</h3><div>There was no association between the duration of at-home transplant hospitalisation and readmissions and the presence of frailty syndrome. Moreover, no patient died due to transplant-related toxicity. The results presented in this study support that at-home auto-HCT can be performed in fit, pre-frail, and frail adults with an experienced and multidisciplinary team. Although conclusions are limited by the reduced sample size, the observed differences on frailty incidences during patient's follow-up support that frailty is dynamic, and potentially amendable with specific interventions.</div></div>","PeriodicalId":9507,"journal":{"name":"Cancer treatment and research communications","volume":"43 ","pages":"Article 100920"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143816380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pembrolizumab after platinum-based chemotherapy for metastatic urothelial cancer: comparison between patients from a Dutch nationwide cohort and KEYNOTE-045","authors":"Anke Richters ,&nbsp;Britt Suelmann ,&nbsp;Mira Franken ,&nbsp;Niven Mehra ,&nbsp;Bart Rikhof ,&nbsp;Hans Westgeest ,&nbsp;Katja Aben ,&nbsp;Debbie Robbrecht","doi":"10.1016/j.ctarc.2025.100931","DOIUrl":"10.1016/j.ctarc.2025.100931","url":null,"abstract":"<div><h3>Background and objective</h3><div>Pending adoption of enfortumab-vedotin plus pembrolizumab in first-line setting, platinum-based chemotherapy remains the standard of care for patients with metastatic or locally advanced urothelial cancer (mUC). Second-line pembrolizumab may be offered to patients with disease progression, based on the KEYNOTE-045 trial. It is unclear how well the findings from KEYNOTE-045 translate to the Dutch mUC patient population in routine clinical practice. The objective of this study was to compare characteristics and outcomes of patients in a nationwide population-based pembrolizumab-treated cohort with the KEYNOTE-045 trial.</div></div><div><h3>Methods</h3><div>A contemporary cohort including all patients diagnosed with synchronous mUC of the bladder from January 2018 - June 2023, treated with platinum-based chemotherapy and subsequent pembrolizumab, was identified from the nationwide Netherlands Cancer Registry and Prospective Bladder Cancer Infrastructure, and compared to the KEYNOTE-045 pembrolizumab (KN-P) arm.</div></div><div><h3>Key findings</h3><div>The Dutch cohort included 249 patients; the full KN-P arm included 270 patients (no overlapping patients). The Dutch cohort comprised more patients with ECOG≥2 (10.3% vs 1.1%), hemoglobin levels &lt;10g/dL (29.8% vs 16.4%), and carboplatin-based chemotherapy (49.0% vs 25.9%). At least 24.5% of patients in the Dutch cohort were KEYNOTE-045 ineligible. Median pembrolizumab duration and overall survival were 2.5 (range &lt;0.1-35.6) and 5.5 months (95%CI: 4.4-7.3) in the Dutch cohort, versus 3.5 (&lt;0.1-20.0) and 10.1 months (95%CI: 8.0-12.3) in the KN-P arm.</div></div><div><h3>Conclusion</h3><div>This nationwide cohort demonstrated considerable differences in patient, disease and treatment characteristics as compared to patients in the KN-P arm, with generally less favorable prognostic characteristics and worse survival. Sensitivity analyses on patients with metachronous mUC or mUC of the upper urinary tract did not alter the findings. These findings highlight the importance of adequate patient selection according to the KEYNOTE-045 criteria while also accounting for disparities between patient populations in routine clinical practice and those in clinical trials.</div></div>","PeriodicalId":9507,"journal":{"name":"Cancer treatment and research communications","volume":"43 ","pages":"Article 100931"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143844759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A retrospective study to investigate the prevalence and describe the clinicopathological characteristics, treatments, and outcomes of HER2-low Breast Cancer in Taiwan","authors":"Kuo-Ting Lee ,&nbsp;Po-Hsiang Huang ,&nbsp;Chih-Yi Hsu ,&nbsp;Yi-Hsuan Lee ,&nbsp;Hui-Wen Chen ,&nbsp;Yen-Shen Lu ,&nbsp;Jiun-I Lai ,&nbsp;Ta-Chung Chao ,&nbsp;Chun-Yu Liu ,&nbsp;Chi-Cheng Huang ,&nbsp;Yi-Fang Tsai ,&nbsp;Ling-Ming Tseng ,&nbsp;Wei-Chen Yang ,&nbsp;Yu-Ting Huang ,&nbsp;Ching-Ya Huang ,&nbsp;Yu-Ciou Lin","doi":"10.1016/j.ctarc.2025.100893","DOIUrl":"10.1016/j.ctarc.2025.100893","url":null,"abstract":"<div><h3>Background</h3><div>The binary classification of human epidermal growth factor receptor 2 (HER2) as HER2-positive [immunohistochemistry (IHC) 2+/in situ hybridization (ISH)+ or 3+] or HER2-negative (IHC 0, 1+, or 2+/ISH-) has been reassessed due to the efficacy of an anti-HER2 antibody-drug conjugate—Trastuzumab Deruxtecan in HER2-low (IHC 1+ or 2+/ISH-) unresectable/metastatic breast cancer (mBC) patients. However, little is known about the prevalence and outcomes of HER2-low mBC in Taiwan.</div></div><div><h3>Methods</h3><div>This retrospective study rescored archived HER2 IHC slides of HER2-negative unresectable/mBC patients diagnosed from 2017 to 2020. The HER2-low prevalence (among HER2-negative), clinicopathological characteristics, treatments, and outcomes of HER2-low unresectable/mBC patients were investigated.</div></div><div><h3>Results</h3><div>Of the rescored HER2-negative cohort, HER2-low prevalence was 61.2 % (186/304) and slightly higher in slides tested by non-Ventana 4B5 assays (vs. Ventana 4B5) and slides from metastatic sites (vs. primary tumors). The overall percentage agreement between historical and rescored IHC was high (90.1 %). For HR+/HER2-low patients, endocrine therapies were frequently used in the first two lines of treatment, while chemotherapy was more common after the second-line treatment. Chemotherapy was the predominant treatment for HR-/HER2-low patients. Time to next treatment (TTNT) and overall survival (OS) since the first-line systemic therapy were longer in the HR+/HER2-low (N = 138) compared to HR-/HER2-low (N = 48) cohorts (median TTNT: 7.6 vs. 4.8 months; median OS: 37.7 vs. 18.8 months).</div></div><div><h3>Conclusion</h3><div>This study suggested that two-thirds of HER2-negative unresectable/mBC patients in Taiwan were HER2-low. Reassessing the HER2 status of HER2-negative patients could improve treatment strategies with the evolving HER2 classification paradigm.</div></div>","PeriodicalId":9507,"journal":{"name":"Cancer treatment and research communications","volume":"43 ","pages":"Article 100893"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143703988","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":"Targeted therapy for non-small cell lung cancer (NSCLC) in a real-world setting: A single practice experience","authors":"Achim Rothe ,&nbsp;Nathalie Bauer ,&nbsp;Lutz Dietze ,&nbsp;Dieter Mainka ,&nbsp;Sonja Lehnert ,&nbsp;Matthias Scheffler","doi":"10.1016/j.ctarc.2025.100891","DOIUrl":"10.1016/j.ctarc.2025.100891","url":null,"abstract":"<div><div>Targeted treatment of non-small cell lung cancer (NSCLC) with driver aberrations has drastically improved the outcome of a subset of patients. However, for successful adaptation in the clinical routine, many stakeholders are involved, like comprehensive cancer centers, molecular pathology, peripheral hospitals, and oncology practices. Here, we present a single center experience in personalized treatment of lung cancer in Germany. Patients with advanced NSCLC and the need for systemic treatment after identification of a targetable driver mutation have been included in this analysis. Detection of the mutations was performed within a diagnostical network. Treatment was chosen depending on the respective driver mutation. We identified 58 patients (26 male, 32 female) with treatment relevant driver mutations: 33 patients (56.9 %) had an <em>EGFR</em> mutation, nine patients (15.5 %) presented with <em>ALK</em> translocation, five patients (8.6 %) were detected to have <em>BRAF</em> mutations, four had <em>ROS1</em> translocations (6.9 %) and 8 patients had <em>MET</em> mutations (13.8 % each). In one patient, concomitant <em>BRAF</em> and <em>MET</em> amplifications were detected. 52 patients received targeted therapy. The median overall survival was 35.5 months (95 % CI, 18.0–52.9 months). 32 patients (64 %) received subsequent treatment after initiation of targeted therapy first-line. Our single-center experience demonstrates that advances in the field of targeted NSCLC therapy are quickly incorporated into clinical routine in Germany. Noteworthy, no new safety information was found.</div></div>","PeriodicalId":9507,"journal":{"name":"Cancer treatment and research communications","volume":"43 ","pages":"Article 100891"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143680846","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":"Treatment refractoriness and response rates in patients with relapsed/refractory multiple myeloma: a retrospective analysis of real-world data","authors":"Ning Lyu,&nbsp;Zahra Majd,&nbsp;Bilqees Fatima,&nbsp;Zhen Zeng,&nbsp;Hua Chen,&nbsp;Susan Abughosh","doi":"10.1016/j.ctarc.2025.100921","DOIUrl":"10.1016/j.ctarc.2025.100921","url":null,"abstract":"<div><h3>Background</h3><div>Significant advancements have been made in the management of multiple myeloma (MM); however, high relapse rates continue to worsen prognosis and reduce survival for many patients. This study aims to evaluate treatment refractoriness and response rates in individuals with relapsed and/or refractory MM using real-world evidence.</div></div><div><h3>Methodology</h3><div>A retrospective cohort study utilizing commercial registry data for 2022, included individuals with relapsed and/or refractory MM who are 18–79 years old and obtain minimum of 5 lines of therapy. Patients at least have one proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and CD38-targeting monoclonal antibody (CD38 MoAB), with their last MM-related visit before October 2022. Patients were excluded if they had concurrent primary malignancies or documented death within 28 days of last line of treatment initiation. Descriptive data, including patient demographic and clinical characteristics, were summarized using continuous and categorical variables.</div></div><div><h3>Results</h3><div>We identified 283 patients after applying inclusion and exclusion criteria. 35.7 % of patients have an overall response rate with median response duration of 6.3 months. Most of patients were found to be categorized in penta-refractory class (33.6 %), followed by triple-refractory (25.4 %), dual-refractory (19.4 %), and not triple-refractory classes (13.4 %). The response rate was 49.1% in dual-class refractory, 22.2 % in triple-class refractory, 44.7 % in not triple-class refractory, and 33.7 % in penta-class refractory patients.</div></div><div><h3>Conclusion</h3><div>Findings imply that substantial proportion of patients continue to show limited treatment response and treatment refractoriness even after multiple lines of therapy.</div></div>","PeriodicalId":9507,"journal":{"name":"Cancer treatment and research communications","volume":"43 ","pages":"Article 100921"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791750","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 evaluation of treatment patterns and clinical outcomes in patients with BRAF-V600E metastatic colorectal cancer (mCRC) in Canada","authors":"William J Phillips ,&nbsp;Horia Marginean ,&nbsp;Mohammad Alrehaili ,&nbsp;Arwa Ahmed Abdelrahim ,&nbsp;Tim Asmis ,&nbsp;Mike Vickers ,&nbsp;Benjamin Yeung ,&nbsp;Bryan Lo ,&nbsp;Rachel Goodwin","doi":"10.1016/j.ctarc.2025.100896","DOIUrl":"10.1016/j.ctarc.2025.100896","url":null,"abstract":"<div><h3>Background</h3><div>BRAF V600E mutations are identified in 10 % of metastatic colorectal cancer (mCRC) cases. In this project, we evaluated the clinicopathologic features and natural history of patients with BRAF mutant (BRAF-mt) mCRC prior to era of BRAF targeted therapy.</div></div><div><h3>Methods</h3><div>This is a retrospective project evaluating patients with diagnosed with mCRC with an identified BRAF V600E mutation between January 1, 2015 and December 31, 2021 seen at the Ottawa Hospital Cancer Centre prior to the approval of cetuximab and encorafenib in Canada. Demographic, clinical, and cancer characteristics were collected from the medical records. Outcomes of interest included overall survival (OS) and time to next therapy (TNT).</div></div><div><h3>Results</h3><div>71 patients were included. The median age was 69 years, 37 (52 %) patients were females, and 19 (27 %) were mismatch repair deficient (dMMR). Median OS was 12.9 months with 21 (30 %) patients living greater than 2-years. Signet ring histology (HR=7.27, <em>p</em> &lt; 0.001), peritoneal metastasis (HR=2.29, 0.003), distant lymphatic metastasis (HR=2.70, <em>p</em> &lt; 0.001), brain metastasis (HR=2.86, <em>p</em> &lt; 0.048) and metastatectomy (HR=0.17, <em>p</em> &lt; 0.001) were associated with OS. Forty-six (65 %) patients received first-line systemic therapy, 14 (20 %) second-line and 2 (3 %) third-line. Median duration of therapy was 8.5 months for first-line, 5.5 months for second-line and 1.5 months for third-line.</div></div><div><h3>Conclusion</h3><div>Real world data demonstrates that patients with BRAF-V600E mCRC have poor clinical outcomes with traditional systemic therapies. Only a minority of patients received second- or third-line systemic treatments, highlighting the importance of ongoing research evaluating incorporation of targeted therapy in first-line treatment.</div></div>","PeriodicalId":9507,"journal":{"name":"Cancer treatment and research communications","volume":"43 ","pages":"Article 100896"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143705711","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":"Whole exome sequencing of low risk endometrial cancer patients with isolated local recurrences","authors":"Shuhua Zheng,&nbsp;Yirong Liu,&nbsp;Paul D. Kinkopf,&nbsp;Amulya Yalamanchili,&nbsp;Jonathan B. Strauss,&nbsp;Eric D. Donnelly","doi":"10.1016/j.ctarc.2025.100890","DOIUrl":"10.1016/j.ctarc.2025.100890","url":null,"abstract":"<div><h3>Introduction</h3><div>A small proportion of clinicopathologically low-risk endometrial cancer (EC) patients who omitted adjuvant radiotherapy (RT) may subsequently develop a local recurrence. Molecular profile for those clinically low-risk yet recurred EC patients is unavailable.</div></div><div><h3>Methods</h3><div>A total of 442 EC patients treated from 2014 to 2020 at Northwestern Memorial Hospital were studied. Among them, 28 patients clinically low risk or low-intermediate risk per GOG-99 criteria developed an isolated local recurrence after hysterectomy, bilateral salpingo-oophorectomy, and omitted RT. Whole exome sequencing (WES) was performed on 22 patients whose pathologic specimen were retrievable.</div></div><div><h3>Results</h3><div>The majority of the cases studied were molecularly No Specific Molecular Profile (NSMP) cohort (91%). We identified <em>CTNNB1, FGFR2, PTEN</em>, and <em>KRAS</em> as the most frequently altered pathogenic or likely pathogenic genes with 5 (22.7%), 5 (22.7%), 4 (18.2%), and 3 (13.6%) out of 22 patients carrying these alterations, respectively. <em>TP53</em> somatic alterations were identified in 2 (9.1%) out of 22 cases. Analysis of The Cancer Genome Atlas Uterine Corpus Endometrial Carcinoma (TCGA-UCEC) dataset identified 53 EC patients with pathologically Grade 1 molecularly NSMP cohort. Within this cohort, <em>CTNNB</em>1 alterations were identified in 31 patients (58%) and prognosticated worse progression free survival (<em>p</em>&lt;0.05).</div></div><div><h3>Conclusion</h3><div>NSMP molecular group constitutes the majority of clinically low-risk EC patients with isolated local recurrences. The <em>CTNNB1</em> alteration was validated as a biomarker in prognostication in this independent cohort and may help guide adjuvant treatment decisions.</div></div>","PeriodicalId":9507,"journal":{"name":"Cancer treatment and research communications","volume":"43 ","pages":"Article 100890"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143628711","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":"Ferroptosis as the new approach to cancer therapy","authors":"Oluwafemi Adeleke Ojo ,&nbsp;Susan Grant ,&nbsp;Pearl Ifunanya Nwafor-Ezeh ,&nbsp;Tobiloba Christiana Maduakolam-Aniobi ,&nbsp;Tolulope Isaiah Akinborode ,&nbsp;Emmanuel Henry Ezenabor ,&nbsp;Adebola Busola Ojo","doi":"10.1016/j.ctarc.2025.100913","DOIUrl":"10.1016/j.ctarc.2025.100913","url":null,"abstract":"<div><div>Cancer is characterized by unregulated cell proliferation, evasion of apoptosis, and a propensity for metastasis, making it a leading cause of morbidity and mortality globally. Major challenges in cancer treatment include drug resistance and tumor heterogeneity, which hinder the clinical efficacy of existing therapies. To enhance treatment outcomes, it is essential to integrate emerging biological insights and technological advancements with conventional therapeutic strategies. Recent research has identified various forms of cell death, which can be classified as either regulated or unregulated. Regulated cell death involves specific biochemical and signaling pathways, while unregulated cell death occurs passively and uncontrollably. Apoptosis, the most extensively studied form of regulated cell death, is primarily mediated by the activation of caspase proteases. Nevertheless, the resistance of many tumors to apoptotic pathways has shifted focus towards non-apoptotic forms of cell death, such as ferroptosis. Ferroptosis is an iron-dependent form of regulated necrosis characterized by extensive membrane damage resulting from lipid peroxidation. Numerous preclinical studies have demonstrated that inducing ferroptosis can significantly reduce tumor growth across a variety of cancer types. For instance, in a study involving breast cancer models, the use of ferroptosis inducers such as erastin and RSL3 led to a marked decrease in tumor volume and weight.</div><div>This review aims to explore the potential of ferroptosis as a novel therapeutic strategy in cancer treatment.</div></div>","PeriodicalId":9507,"journal":{"name":"Cancer treatment and research communications","volume":"43 ","pages":"Article 100913"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143776820","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":"Targeting the phosphatidylinositol-3-kinase (PI3K) and mitogen activated protein kinase (MAPK) signalling pathways to enhance chemoradiotherapy in locally advanced rectal cancer","authors":"Aoife Carr ,&nbsp;Jonathan A. Coulter ,&nbsp;Julie Workman ,&nbsp;Joanna Fay ,&nbsp;Angela Farrelly ,&nbsp;Alex J. Eustace ,&nbsp;Lindsey Bennie ,&nbsp;Liam Grogan ,&nbsp;Oscar Breathnach ,&nbsp;Patrick G. Morris ,&nbsp;Deborah A. McNamara ,&nbsp;Mattia Cremona ,&nbsp;Brian D.P. O'Neill ,&nbsp;Bryan T. Hennessy ,&nbsp;Sinead Toomey","doi":"10.1016/j.ctarc.2025.100926","DOIUrl":"10.1016/j.ctarc.2025.100926","url":null,"abstract":"<div><div>Responses to neoadjuvant chemoradiotherapy for locally advanced rectal cancer are not uniform. The phosphatidylinositol-3 kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways are involved in tumorigenesis and treatment resistance in many cancers; therefore, targeting these pathways could enhance response to chemoradiotherapy.</div><div>A panel of colorectal cancer (CRC) cell lines (<em>n</em> = 10) with varying PI3K and MAPK mutational backgrounds were treated with combinations of 5-Flourouracil (5-FU), radiation, the PI3K inhibitor copanlisib, and/or the MEK inhibitor refametinib, and their effects on proliferation <em>in vitro</em> were measured. BALB/c SCID mice were implanted with CRC cell lines representative of each mutational background, treated with copanlisib and/or chemoradiotherapy, and monitored for tumor growth.</div><div><em>In vitro, PIK3CA</em> mutated cell lines were most sensitive to copanlisib (IC50=28 nM) and <em>KRAS</em> mutated cell lines were most sensitive to refametinib (IC50 = 36 nM), while the combination of copanlisib and refametinib was synergistic in 9/10 cell lines tested. The addition of copanlisib to 5-FU chemoradiotherapy inhibited cell growth compared to 5-FU chemoradiotherapy alone, an effect that was most notable in LS-1034 (<em>KRAS</em> mutated) and Caco-2 (<em>PIK3CA/KRAS</em> wild-type) cell lines. <em>In vivo</em> copanlisib and 5-FU chemoradiotherapy reduced tumor growth in all xenograft models and increased overall survival in LS-1034 and Caco-2 xenografts.</div><div>Our results suggest that activation of the kinase signalling pathway may modulate PI3K/MEK inhibitor responsiveness in colorectal cancer. Furthermore, the addition of copanlisib to 5-FU chemoradiotherapy resulted in an enhanced anti-proliferative cytotoxic effect compared to 5-FU chemoradiotherapy alone, regardless of the background mutational status, and supports further clinical development of this regimen.</div></div>","PeriodicalId":9507,"journal":{"name":"Cancer treatment and research communications","volume":"43 ","pages":"Article 100926"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143837840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}