Min Tang, Binle Tian, Jingyi Zhou, Di Ma, Rongze Sun, Qi Li
Objective
Krüppel-like factor 4 (KLF4) is a zinc finger transcription factor that plays context-dependent roles in cancer. It functions as either a tumor suppressor or an oncogene depending on tumor type and cellular context. This review aimed to comprehensively summarize the roles of KLF4 in the tumor microenvironment (TME) and evaluate its potential as a therapeutic target.
Methods
We conducted a comprehensive literature review to elucidate the expression patterns, regulatory mechanisms, and functional roles of KLF4 across different TME components, including cancer cells, immune cells, cancer-associated fibroblasts, pericytes, and extracellular matrix.
Results
KLF4 exhibits dual roles in cancer cells, acting as a tumor suppressor in gastric, lung, and pancreatic cancers while promoting oncogenesis in breast, colorectal, and prostate cancers. In the TME, KLF4 regulates macrophage polarization (M1/M2), T-cell exhaustion, NK cell activity, and MDSC recruitment. Additionally, KLF4 modulates CAF activation and ECM remodeling. KLF4 expression is regulated by miRNAs, lncRNAs, and epigenetic modifications. Emerging therapeutic strategies targeting KLF4, such as APTO-253, show promise in preclinical and early clinical trials.
Conclusions
KLF4 serves as a hub gate orchestrating cell crosstalk within the TME. Understanding its context-dependent functions may facilitate the development of KLF4-targeted therapies for precision oncology.
{"title":"Krüppel-Like Factor 4, a Hub Gate for Cell Crosstalk in Tumor Microenvironment","authors":"Min Tang, Binle Tian, Jingyi Zhou, Di Ma, Rongze Sun, Qi Li","doi":"10.1002/cam4.71498","DOIUrl":"10.1002/cam4.71498","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Krüppel-like factor 4 (KLF4) is a zinc finger transcription factor that plays context-dependent roles in cancer. It functions as either a tumor suppressor or an oncogene depending on tumor type and cellular context. This review aimed to comprehensively summarize the roles of KLF4 in the tumor microenvironment (TME) and evaluate its potential as a therapeutic target.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a comprehensive literature review to elucidate the expression patterns, regulatory mechanisms, and functional roles of KLF4 across different TME components, including cancer cells, immune cells, cancer-associated fibroblasts, pericytes, and extracellular matrix.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>KLF4 exhibits dual roles in cancer cells, acting as a tumor suppressor in gastric, lung, and pancreatic cancers while promoting oncogenesis in breast, colorectal, and prostate cancers. In the TME, KLF4 regulates macrophage polarization (M1/M2), T-cell exhaustion, NK cell activity, and MDSC recruitment. Additionally, KLF4 modulates CAF activation and ECM remodeling. KLF4 expression is regulated by miRNAs, lncRNAs, and epigenetic modifications. Emerging therapeutic strategies targeting KLF4, such as APTO-253, show promise in preclinical and early clinical trials.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>KLF4 serves as a hub gate orchestrating cell crosstalk within the TME. Understanding its context-dependent functions may facilitate the development of KLF4-targeted therapies for precision oncology.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12800926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145964894","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}
MET aberrations are capable of triggering oncogenesis through multiple clinical significance genomic alterations. In non-small cell lung cancer, MET exon 14 skipping and MET amplification confer sensitivity to MET tyrosine kinase inhibitors. The MET gene is also one of the druggable genes in high-grade gliomas. However, a systematic comparison of MET variations between lung cancer and brain tumors is lacking.
Methods
We analyzed a large Chinese cohort of 30,355 lung cancer and 6004 brain tumor patients. Different MET mutation types were characterized, and somatic genomic mutational characteristics were examined across various MET mutation subgroups in both lung cancer and brain tumor cohorts. The impact of MET mutations on prognosis in these two cohorts was also assessed. The study cohort underwent comprehensive genomic profiling using targeted next-generation sequencing (NGS) panels.
Results
We found that clinically significant MET mutations exist in both lung and brain tumor cohorts, with the lung cancer group having a higher overall frequency (p < 0.001), but the frequency of different MET mutation types, mutation characteristics, tumor mutation burden, and co-mutated genes with high frequency all differ. MET alterations were significantly enriched in post-treatment brain tumors (8.5% vs. 4.8% in treatment-naïve, p < 0.001). MET mutations also have different prognostic effects in the two cancer types. MET alterations were not prognostic in lung cancer but were associated with significantly poorer survival in brain tumors (median OS: 19.9 vs. 62.9 months, p < 0.001), a finding that held in multivariate analysis.
Conclusions
Our study demonstrated that the biological and clinical significance of MET alterations is highly context dependent. In lung cancer, MET serves primarily as a predictive biomarker for targeted therapy, whereas in brain tumors, it functions as a prognostic marker of genomic instability and aggressive disease. These findings advocate for context-specific clinical management strategies.
{"title":"The Mutation Patterns of MET Gene in Lung Cancer and Brain Tumors: Clinical and Therapeutic Implications","authors":"Yu Zhang, Ningning Luo, Minghui Ge, Yanxiang Zhang, Dongsheng Chen, Yongmeng Li","doi":"10.1002/cam4.71532","DOIUrl":"10.1002/cam4.71532","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p><i>MET</i> aberrations are capable of triggering oncogenesis through multiple clinical significance genomic alterations. In non-small cell lung cancer, <i>MET</i> exon 14 skipping and <i>MET</i> amplification confer sensitivity to MET tyrosine kinase inhibitors. The <i>MET</i> gene is also one of the druggable genes in high-grade gliomas. However, a systematic comparison of <i>MET</i> variations between lung cancer and brain tumors is lacking.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analyzed a large Chinese cohort of 30,355 lung cancer and 6004 brain tumor patients. Different <i>MET</i> mutation types were characterized, and somatic genomic mutational characteristics were examined across various <i>MET</i> mutation subgroups in both lung cancer and brain tumor cohorts. The impact of <i>MET</i> mutations on prognosis in these two cohorts was also assessed. The study cohort underwent comprehensive genomic profiling using targeted next-generation sequencing (NGS) panels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found that clinically significant <i>MET</i> mutations exist in both lung and brain tumor cohorts, with the lung cancer group having a higher overall frequency (<i>p</i> < 0.001), but the frequency of different <i>MET</i> mutation types, mutation characteristics, tumor mutation burden, and co-mutated genes with high frequency all differ. <i>MET</i> alterations were significantly enriched in post-treatment brain tumors (8.5% vs. 4.8% in treatment-naïve, <i>p</i> < 0.001). <i>MET</i> mutations also have different prognostic effects in the two cancer types. <i>MET</i> alterations were not prognostic in lung cancer but were associated with significantly poorer survival in brain tumors (median OS: 19.9 vs. 62.9 months, <i>p</i> < 0.001), a finding that held in multivariate analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our study demonstrated that the biological and clinical significance of <i>MET</i> alterations is highly context dependent. In lung cancer, <i>MET</i> serves primarily as a predictive biomarker for targeted therapy, whereas in brain tumors, it functions as a prognostic marker of genomic instability and aggressive disease. These findings advocate for context-specific clinical management strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12793781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145950815","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}
Masaaki Hotta, Atsushi Satake, Ayako Iwama, Tokiko Hoshiyama, Yukie Tsubokura, Hideaki Yoshimura, Shinya Fujita, Yumiko Kono, Tomoki Ito
Background
PV-R-CHP (polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, and prednisone) is a recently introduced regimen for untreated diffuse large B-cell lymphoma (DLBCL). However, real-world data comparing its efficacy and safety with those of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) remain limited.
Aims
This study aimed to evaluate the real-world efficacy and safety of PV-R-CHP compared with R-CHOP-based regimens in patients with newly diagnosed DLBCL.
Materials and Methods
We conducted a retrospective analysis of patients with DLBCL who received PV-R-CHP or R-CHOP-based treatment as first-line therapy at Kansai Medical University Hospital between January 2020 and August 2023. The primary endpoint was progression-free survival (PFS). Other outcomes included overall survival (OS), treatment response, subgroup analyses, and adverse events. Propensity score matching was performed, and prespecified subgroup analyses were conducted in the matched cohort.
Results
A total of 153 patients were included: 53 received PV-R-CHP and 100 received R-CHOP. At 1 year, both PFS and OS were significantly higher in the PV-R-CHP group than in the R-CHOP group (PFS: 89.3% vs. 70.9%, hazard ratio [HR] 0.30 [95% confidence interval (CI): 0.12–0.78], p = 0.013; OS: 92.5% vs. 80.0%, HR 0.28 [95% CI: 0.08–0.95], p = 0.041). Complete response rates were comparable between the groups (81.1% vs. 76.0%, p = 0.543). In propensity score–matched analyses, PV-R-CHP was associated with improved PFS in patients with non–germinal center B-cell–like (non-GCB) DLBCL. The incidence of grade ≥ 3 adverse events was similar between the regimens, with lymphopenia being the most frequent toxicity.
Conclusion
PV-R-CHP may offer improved survival outcomes compared with R-CHOP in newly diagnosed DLBCL, particularly in patients with non-GCB, with an acceptable safety profile in a real-world setting. Although longer follow-up is required to confirm durability, these findings support the use of PV-R-CHP as a frontline treatment option.
背景：PV-R-CHP （polatuzumab vedotin、利妥昔单抗、环磷酰胺、阿霉素和泼尼松）是最近引入的一种治疗未经治疗的弥漫性大b细胞淋巴瘤（DLBCL）的方案。然而，将其与R-CHOP（利妥昔单抗、环磷酰胺、阿霉素、长春新碱和强的松）的疗效和安全性进行比较的实际数据仍然有限。目的：本研究旨在评估PV-R-CHP与r - chop为基础的方案在新诊断的DLBCL患者中的实际疗效和安全性。材料和方法：我们对2020年1月至2023年8月在关西医科大学医院接受PV-R-CHP或r - chop为一线治疗的DLBCL患者进行了回顾性分析。主要终点为无进展生存期（PFS）。其他结果包括总生存期（OS）、治疗反应、亚组分析和不良事件。进行倾向评分匹配，并在匹配的队列中进行预先指定的亚组分析。结果：共纳入153例患者，其中PV-R-CHP 53例，R-CHOP 100例。1年时，PV-R-CHP组的PFS和OS均显著高于R-CHOP组(PFS: 89.3% vs. 70.9%，风险比[HR] 0.30[95%可信区间（CI）： 0.12-0.78], p = 0.013；操作系统:92.5%比80.0%,人力资源0.28(95%置信区间:0.08—-0.95),p = 0.041)。两组间完全缓解率具有可比性（81.1% vs. 76.0%, p = 0.543）。在倾向评分匹配分析中，PV-R-CHP与非生发中心b细胞样（non-GCB） DLBCL患者PFS改善相关。≥3级不良事件的发生率在两种方案之间相似，淋巴细胞减少是最常见的毒性。结论：在新诊断的DLBCL中，PV-R-CHP可能比R-CHOP提供更好的生存结果，特别是在非gcb患者中，在现实环境中具有可接受的安全性。虽然需要更长的随访时间来确认持久性，但这些发现支持将PV-R-CHP作为一线治疗选择。
{"title":"Real-World Outcomes of Polatuzumab Vedotin Plus R-CHP Versus R-CHOP-Based Regimens in Japanese Patients With Untreated Diffuse Large B-Cell Lymphoma","authors":"Masaaki Hotta, Atsushi Satake, Ayako Iwama, Tokiko Hoshiyama, Yukie Tsubokura, Hideaki Yoshimura, Shinya Fujita, Yumiko Kono, Tomoki Ito","doi":"10.1002/cam4.71531","DOIUrl":"10.1002/cam4.71531","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>PV-R-CHP (polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, and prednisone) is a recently introduced regimen for untreated diffuse large B-cell lymphoma (DLBCL). However, real-world data comparing its efficacy and safety with those of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) remain limited.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This study aimed to evaluate the real-world efficacy and safety of PV-R-CHP compared with R-CHOP-based regimens in patients with newly diagnosed DLBCL.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>We conducted a retrospective analysis of patients with DLBCL who received PV-R-CHP or R-CHOP-based treatment as first-line therapy at Kansai Medical University Hospital between January 2020 and August 2023. The primary endpoint was progression-free survival (PFS). Other outcomes included overall survival (OS), treatment response, subgroup analyses, and adverse events. Propensity score matching was performed, and prespecified subgroup analyses were conducted in the matched cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 153 patients were included: 53 received PV-R-CHP and 100 received R-CHOP. At 1 year, both PFS and OS were significantly higher in the PV-R-CHP group than in the R-CHOP group (PFS: 89.3% vs. 70.9%, hazard ratio [HR] 0.30 [95% confidence interval (CI): 0.12–0.78], <i>p</i> = 0.013; OS: 92.5% vs. 80.0%, HR 0.28 [95% CI: 0.08–0.95], <i>p</i> = 0.041). Complete response rates were comparable between the groups (81.1% vs. 76.0%, <i>p</i> = 0.543). In propensity score–matched analyses, PV-R-CHP was associated with improved PFS in patients with non–germinal center B-cell–like (non-GCB) DLBCL. The incidence of grade ≥ 3 adverse events was similar between the regimens, with lymphopenia being the most frequent toxicity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>PV-R-CHP may offer improved survival outcomes compared with R-CHOP in newly diagnosed DLBCL, particularly in patients with non-GCB, with an acceptable safety profile in a real-world setting. Although longer follow-up is required to confirm durability, these findings support the use of PV-R-CHP as a frontline treatment option.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12793779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145950870","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}
Ellenor Chi, Derek K. Chang, Chun-Pin Esther Chang, Seungmin Kim, Jihye Park, John Snyder, Vikrant Deshmukh, Michael G. Newman, Catherine J. Lee, Mia Hashibe
Purpose
Advancing therapies have increased B-cell Non-Hodgkin's Lymphoma (B-NHL) patient survival. However, data are limited on the risk of type II diabetes mellitus (type II DM) in adult survivors following treatment. This study examines the risk of type II DM among a Utah population of B-NHL survivors, compared to the general population.
Methods
A cohort of 3529 adult survivors diagnosed with B-NHL in Utah between 1997 and 2013 in the Utah Cancer Registry and 13,339 individuals from the general population were identified using the Utah Population Database (UPDB). Multivariate Cox Proportional Hazard models were used to estimate adjusted hazard ratios (aHR) for developing type II DM, stratified for time post-diagnosis.
Results
Compared to the cancer-free population, B-NHL survivors had an overall increased risk of developing type II DM (HR: 1.49; 95% CI: 1.32, 1.69), largely within the first year (HR: 4.41; 95% CI: 3.52, 5.52) following diagnosis. Older B-NHL survivors were more likely to develop type II DM at any time compared to survivors < 40 years [40–65 years (HR: 2.66; 95% CI 1.48–4.79); ≥ 65 years (HR: 3.77; 95% CI 2.09–6.78)]. Obese (BMI > 30 kg/m2) survivors had a 4.06-fold increase in the risk of type II DM compared to normal BMI (18–24.9 kg/m2) cancer survivors. Cancer treatment did not increase the risk of type II DM compared to no treatment.
Conclusions
Adult B-NHL cancer survivors were at an overall increased risk of developing type II DM compared to the general population, within the first year and overall, following a cancer diagnosis. This study provides evidence suggesting the importance of obesity prevention and improvement in care management oversight for B-NHL survivorship and DM outcomes.
{"title":"Risk of Type II Diabetes Mellitus Among B-Cell Non-Hodgkin's Lymphoma Survivors","authors":"Ellenor Chi, Derek K. Chang, Chun-Pin Esther Chang, Seungmin Kim, Jihye Park, John Snyder, Vikrant Deshmukh, Michael G. Newman, Catherine J. Lee, Mia Hashibe","doi":"10.1002/cam4.71367","DOIUrl":"10.1002/cam4.71367","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>Advancing therapies have increased B-cell Non-Hodgkin's Lymphoma (B-NHL) patient survival. However, data are limited on the risk of type II diabetes mellitus (type II DM) in adult survivors following treatment. This study examines the risk of type II DM among a Utah population of B-NHL survivors, compared to the general population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A cohort of 3529 adult survivors diagnosed with B-NHL in Utah between 1997 and 2013 in the Utah Cancer Registry and 13,339 individuals from the general population were identified using the Utah Population Database (UPDB). Multivariate Cox Proportional Hazard models were used to estimate adjusted hazard ratios (aHR) for developing type II DM, stratified for time post-diagnosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Compared to the cancer-free population, B-NHL survivors had an overall increased risk of developing type II DM (HR: 1.49; 95% CI: 1.32, 1.69), largely within the first year (HR: 4.41; 95% CI: 3.52, 5.52) following diagnosis. Older B-NHL survivors were more likely to develop type II DM at any time compared to survivors < 40 years [40–65 years (HR: 2.66; 95% CI 1.48–4.79); ≥ 65 years (HR: 3.77; 95% CI 2.09–6.78)]. Obese (BMI > 30 kg/m<sup>2</sup>) survivors had a 4.06-fold increase in the risk of type II DM compared to normal BMI (18–24.9 kg/m<sup>2</sup>) cancer survivors. Cancer treatment did not increase the risk of type II DM compared to no treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Adult B-NHL cancer survivors were at an overall increased risk of developing type II DM compared to the general population, within the first year and overall, following a cancer diagnosis. This study provides evidence suggesting the importance of obesity prevention and improvement in care management oversight for B-NHL survivorship and DM outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12793787/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145950878","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}
Kassem S. Faraj, Mary Oerline, Samuel R. Kaufman, Christopher Dall, Arnav Srivastava, Xiu Liu, Megan E. V. Caram, Vahakn B. Shahinian, Brent K. Hollenbeck
Introduction
A paradigm shift in advanced prostate cancer toward the use of oral specialty drugs has been accompanied by increased involvement of urologists. In fact, some urology groups can deliver these medications in the office, providing them directly to their patients.
Methods
A retrospective cohort study was performed using a 20% national sample of men with advanced prostate cancer enrolled in Traditional Medicare and managed by independent urology groups between 2011 and 2019. Urology groups with and without in-office dispensing were identified. Multivariable logistic regression was used to assess relationships between urology group characteristics and in-office dispensing. A difference-in-differences design was used to measure the effect of in-office dispensing on the use of oral specialty drugs within urology group markets compared to markets without dispensing.
Results
Urology group characteristics associated with adoption of in-office dispensing included large practice size (OR 2.9, 95% CI 1.2–6.5), increasing volume of men with advanced prostate cancer (OR 1.1 per 10-patient increase, 95% CI 1.0–1.2), decreasing social vulnerability of the group's patient population (OR 0.81 per 0.1 unit increase, 95% CI 0.69–0.95), lower competition (OR 1.02 per 100 unit increase in the Herfindahl–Hirschman Index, 95% CI 1.0–1.1), and radiation vault ownership (OR 3.1, 95% CI 1.1–8.4). Compared with markets of urology groups that did not adopt in-office dispensing, adopting markets experienced a significant increase in oral specialty drug prescriptions (adjusted difference-in-differences estimate, 46 prescriptions per 1000 men, p < 0.001).
Conclusions
Adoption of in-office dispensing by independent urology groups increased oral specialty drug prescriptions for advanced prostate cancer within a group's market.
{"title":"Impact of In-Office Dispensing Adoption by Urology Practices on Oral Specialty Drug Use in Advanced Prostate Cancer","authors":"Kassem S. Faraj, Mary Oerline, Samuel R. Kaufman, Christopher Dall, Arnav Srivastava, Xiu Liu, Megan E. V. Caram, Vahakn B. Shahinian, Brent K. Hollenbeck","doi":"10.1002/cam4.71475","DOIUrl":"10.1002/cam4.71475","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>A paradigm shift in advanced prostate cancer toward the use of oral specialty drugs has been accompanied by increased involvement of urologists. In fact, some urology groups can deliver these medications in the office, providing them directly to their patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A retrospective cohort study was performed using a 20% national sample of men with advanced prostate cancer enrolled in Traditional Medicare and managed by independent urology groups between 2011 and 2019. Urology groups with and without in-office dispensing were identified. Multivariable logistic regression was used to assess relationships between urology group characteristics and in-office dispensing. A difference-in-differences design was used to measure the effect of in-office dispensing on the use of oral specialty drugs within urology group markets compared to markets without dispensing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Urology group characteristics associated with adoption of in-office dispensing included large practice size (OR 2.9, 95% CI 1.2–6.5), increasing volume of men with advanced prostate cancer (OR 1.1 per 10-patient increase, 95% CI 1.0–1.2), decreasing social vulnerability of the group's patient population (OR 0.81 per 0.1 unit increase, 95% CI 0.69–0.95), lower competition (OR 1.02 per 100 unit increase in the Herfindahl–Hirschman Index, 95% CI 1.0–1.1), and radiation vault ownership (OR 3.1, 95% CI 1.1–8.4). Compared with markets of urology groups that did not adopt in-office dispensing, adopting markets experienced a significant increase in oral specialty drug prescriptions (adjusted difference-in-differences estimate, 46 prescriptions per 1000 men, <i>p</i> < 0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Adoption of in-office dispensing by independent urology groups increased oral specialty drug prescriptions for advanced prostate cancer within a group's market.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12791029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145950855","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}
Alíxida Ramos-Pibernus, Mario Bermonti-Pérez, David Mejías-Serrano, Fabián Moreta-Ávila, Paola Carminelli-Corretjer, Nelmit Tollinchi-Natali, Malynie Blanco, Lellanes Justiz, Marta Febo, Matthew B. Schabath, Ash B. Alpert, Eliut Rivera-Segarra
Introduction
Trans men and non-binary people face some of the most challenging cancer health disparities. Primary care physicians could play a key in addressing these, but many clinicians' lack the necessary skill to discuss cervical screening with trans people as these are not routinely taught in medical school. Thus, the objective of this study was to develop an intervention to foster medical students' skills for cervical cancer screening and to examine its initial impact and feasibility.
Methods
Our research team is comprised of academic researchers, clinicians, and community members. Together, we developed a 2-h intervention which we implemented using Standardized Patient Simulations (TM actors portraying the role of a TM patient) to observe provider behaviors (general care behaviors, gender affirming behaviors and cervical cancer preventive behaviors) and self-reported measures to examine study outcomes. The total sample consisted of 37 third-year medical students. Welch's t-test was used to compare the intervention effects on all outcomes.
Results
Results suggest the intervention had medium to large effects on all examined behaviors. Behaviors improved in the experimental group compared to the control group and all changes were statistically significant. In general, the intervention was seen as feasible and appropriate with participants mentioning it was “very helpful” and emphasizing the importance of discussing trans health care as part of their medical training as this improves their “confidence.”
Discussion
Although the sample size was small, results show a potentially promising intervention. We provide an overview of the content of the intervention and discuss future research directions.
{"title":"Development of a Culturally Sensitive Intervention for Cervical Cancer Screening Promotion for Latinx Transgender Individuals","authors":"Alíxida Ramos-Pibernus, Mario Bermonti-Pérez, David Mejías-Serrano, Fabián Moreta-Ávila, Paola Carminelli-Corretjer, Nelmit Tollinchi-Natali, Malynie Blanco, Lellanes Justiz, Marta Febo, Matthew B. Schabath, Ash B. Alpert, Eliut Rivera-Segarra","doi":"10.1002/cam4.71494","DOIUrl":"10.1002/cam4.71494","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Trans men and non-binary people face some of the most challenging cancer health disparities. Primary care physicians could play a key in addressing these, but many clinicians' lack the necessary skill to discuss cervical screening with trans people as these are not routinely taught in medical school. Thus, the objective of this study was to develop an intervention to foster medical students' skills for cervical cancer screening and to examine its initial impact and feasibility.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Our research team is comprised of academic researchers, clinicians, and community members. Together, we developed a 2-h intervention which we implemented using Standardized Patient Simulations (TM actors portraying the role of a TM patient) to observe provider behaviors (general care behaviors, gender affirming behaviors and cervical cancer preventive behaviors) and self-reported measures to examine study outcomes. The total sample consisted of 37 third-year medical students. Welch's <i>t</i>-test was used to compare the intervention effects on all outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Results suggest the intervention had medium to large effects on all examined behaviors. Behaviors improved in the experimental group compared to the control group and all changes were statistically significant. In general, the intervention was seen as feasible and appropriate with participants mentioning it was “very helpful” and emphasizing the importance of discussing trans health care as part of their medical training as this improves their “confidence.”</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>Although the sample size was small, results show a potentially promising intervention. We provide an overview of the content of the intervention and discuss future research directions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12793046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145950837","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}
Stephan Jahn, Katarina Krajina, Maria Anna Smolle, Dimyana Neufeldt, Katharina Jonas, Beate Rinner, Kevin Mellert, Maxim Noeparast, Martin Trepel, Joanna Szkandera, Martin Pichler, Bernadette Liegl-Azwanger
Background
Long non-coding RNA (lncRNA) H19 plays a pivotal role in the pathogenesis of different human cancers, but its role in soft tissue sarcoma (STS) has not yet been defined.
Methods
We analyzed H19 expression patterns in various cancer cell lines, focusing on sarcoma subtypes. RNA in situ hybridization was performed on a tissue microarray (n = 150) to assess H19 expression in human STS samples. Univariate and multivariate analyses were conducted to evaluate H19's prognostic value. In STS cell lines with high H19 expression, a Gapmer-based knock-down approach was used to study the functional impact of H19 expression.
Results
Low H19 expression was associated with poor prognosis in univariate analysis (HR: 0.564; 95% CI: 0.324–0.985; p = 0.044). Multivariate analysis showed advanced patient age (p < 0.001) and large tumor size (p = 0.002) as independent predictors of worse overall survival, irrespective of H19 expression (HR: 0.655; 95% CI: 0.367–1.170; p = 0.153). H19 knockdown in STS cell lines reduced cellular growth and increased pro-apoptotic activity.
Discussion
Our findings suggest that H19 might play a role in STS pathogenesis. While its prognostic value requires further investigation, H19-based targeting approaches may warrant evaluation for therapeutic potential in STS.
{"title":"Clinical Significance and Therapeutic Potential of Long Non-Coding RNA H19 in Soft Tissue Sarcoma","authors":"Stephan Jahn, Katarina Krajina, Maria Anna Smolle, Dimyana Neufeldt, Katharina Jonas, Beate Rinner, Kevin Mellert, Maxim Noeparast, Martin Trepel, Joanna Szkandera, Martin Pichler, Bernadette Liegl-Azwanger","doi":"10.1002/cam4.71305","DOIUrl":"10.1002/cam4.71305","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Long non-coding RNA (lncRNA) H19 plays a pivotal role in the pathogenesis of different human cancers, but its role in soft tissue sarcoma (STS) has not yet been defined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analyzed H19 expression patterns in various cancer cell lines, focusing on sarcoma subtypes. RNA in situ hybridization was performed on a tissue microarray (<i>n</i> = 150) to assess H19 expression in human STS samples. Univariate and multivariate analyses were conducted to evaluate H19's prognostic value. In STS cell lines with high H19 expression, a Gapmer-based knock-down approach was used to study the functional impact of H19 expression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Low H19 expression was associated with poor prognosis in univariate analysis (HR: 0.564; 95% CI: 0.324–0.985; <i>p</i> = 0.044). Multivariate analysis showed advanced patient age (<i>p</i> < 0.001) and large tumor size (<i>p</i> = 0.002) as independent predictors of worse overall survival, irrespective of H19 expression (HR: 0.655; 95% CI: 0.367–1.170; <i>p</i> = 0.153). H19 knockdown in STS cell lines reduced cellular growth and increased pro-apoptotic activity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>Our findings suggest that H19 might play a role in STS pathogenesis. While its prognostic value requires further investigation, H19-based targeting approaches may warrant evaluation for therapeutic potential in STS.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12790950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145950858","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}
Douglas Adkins, Jessica C. Ley, Christine Auberle, Brendan Knapp, Jesse Zaretsky, Jingxia Liu, Peter Oppelt
<div> <section> <h3> Introduction</h3> <p>Standard therapy for PD-1 inhibitor-refractory recurrent or metastatic head and neck squamous-cell carcinoma (RM-HNSCC) has limited activity. Drugs bound to albumin selectively target cancer cells with upregulated macropinocytosis, a process driven by constitutively hyper-activated EGFR/RAS/PIK3CA signaling, which is common in HNSCC. Nanoparticle albumin-bound (<i>nab</i>)-paclitaxel is active in PD-1 inhibitor-naïve RM-HNSCC and alters immune cells to potentially prime tumor response and reverse resistance to PD-1 inhibitors.</p> </section> <section> <h3> Methods</h3> <p>In a single-arm phase 2 trial, patients with PD-1 inhibitor-refractory RM-HNSCC received <i>nab-</i>paclitaxel and nivolumab given in 28-day cycles. The primary endpoint was objective response rate (ORR), using RECIST1.1. Key secondary endpoints were duration of response (DoR), progression-free survival (PFS), and overall survival (OS). At least one tumor response assessment was required to be evaluable for ORR and PFS. A Simon optimal two-stage design tested the primary hypothesis (ORR: H<sub>1</sub> ≥ 50 vs. H<sub>0</sub> ≤ 30%, type I error 0.05; power 0.80). H<sub>0</sub> was rejected if ≥ 19 responses were observed in 46 patients. This sample size had a power of 80% to detect the difference in the key secondary hypothesis (median PFS: H<sub>1</sub> 6.0 vs. H<sub>0</sub> 3.6 months, two-sided, one-sample log rank test; type I error 0.05).</p> </section> <section> <h3> Results</h3> <p>From 9/28/2021–1/4/2024, 46 patients enrolled into the trial. One patient was not evaluable for ORR and PFS. Tumor response occurred in 21 of 45 evaluable patients (ORR 46.7%, 95% CI: 33.8–59.9; vs. H<sub>0</sub>, <i>p</i> = 0.0073) and included confirmed response in 20 and unconfirmed response in 1. The best tumor response was complete (4), partial (17), stable (18), and progression (6). The median DoR was 6.1 months (95% CI: 2.8–9.4). With a median follow-up of 14.1 months (IQR: 7.6–20.1), the median PFS was 5.5 months (95% CI: 3.9–7.8) and the median OS was 13.9 months (95% CI: 9.0–18.9). Treatment-related deaths did not occur.</p> </section> <section> <h3> Conclusion</h3> <p>Among patients with PD-1 inhibitor-refractory RM-HNSCC, <i>nab</i>-paclitaxel and nivolumab resulted in an ORR and median PFS that were better than historically reported with standard therapy.</p> </section> <section> <h3> Trial Registration</h3> <p>Trial registered on www.clinical
PD-1抑制剂难治性复发或转移性头颈部鳞状细胞癌（RM-HNSCC）的标准治疗活性有限。与白蛋白结合的药物选择性靶向巨噬细胞增多症上调的癌细胞，这是一个由组成性超激活的EGFR/RAS/PIK3CA信号驱动的过程，这在HNSCC中很常见。纳米颗粒白蛋白结合(nab)-紫杉醇在PD-1 inhibitor-naïve RM-HNSCC中具有活性，并改变免疫细胞，潜在地引发肿瘤反应并逆转对PD-1抑制剂的耐药性。方法：在一项单组2期试验中，PD-1抑制剂难治性RM-HNSCC患者接受了nab-紫杉醇和纳武单抗，周期为28天。主要终点是客观缓解率（ORR），使用RECIST1.1。关键的次要终点是反应持续时间（DoR）、无进展生存期（PFS）和总生存期（OS）。至少需要一项肿瘤反应评估来评估ORR和PFS。Simon最优两阶段设计检验了主要假设（ORR: H1≥50 vs. H0≤30%，I型误差0.05；功率0.80）。如果在46例患者中观察到≥19个应答，则H0被拒绝。该样本量具有80%的能力来检测关键次要假设的差异（中位PFS: H1 6.0 vs. H0 3.6个月，双侧，单样本对数秩检验；I型误差0.05）。结果：从2021年9月28日至2024年1月4日，46例患者入组试验。1例患者的ORR和PFS无法评估。45例可评估患者中有21例出现肿瘤缓解（ORR 46.7%, 95% CI: 33.8-59.9; vs. H0, p = 0.0073），其中20例确诊缓解，1例未确诊缓解。最佳的肿瘤反应是完全(4)、部分（17）、稳定（18）和进展(6)。中位DoR为6.1个月（95% CI: 2.8-9.4）。中位随访14.1个月（IQR: 7.6-20.1），中位PFS为5.5个月（95% CI: 3.9-7.8），中位OS为13.9个月（95% CI: 9.0-18.9）。治疗相关死亡未发生。结论：在PD-1抑制剂难治性RM-HNSCC患者中，nab-紫杉醇和纳沃单抗导致的ORR和中位PFS优于历史上报道的标准治疗。试验注册：在www.Clinicaltrials: gov上注册试验，国家临床试验（NCT） 04831320。
{"title":"Nanoparticle Albumin-Bound Paclitaxel and Nivolumab for PD-1 Inhibitor-Refractory Recurrent or Metastatic Head and Neck Squamous-Cell Carcinoma","authors":"Douglas Adkins, Jessica C. Ley, Christine Auberle, Brendan Knapp, Jesse Zaretsky, Jingxia Liu, Peter Oppelt","doi":"10.1002/cam4.71533","DOIUrl":"10.1002/cam4.71533","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Standard therapy for PD-1 inhibitor-refractory recurrent or metastatic head and neck squamous-cell carcinoma (RM-HNSCC) has limited activity. Drugs bound to albumin selectively target cancer cells with upregulated macropinocytosis, a process driven by constitutively hyper-activated EGFR/RAS/PIK3CA signaling, which is common in HNSCC. Nanoparticle albumin-bound (<i>nab</i>)-paclitaxel is active in PD-1 inhibitor-naïve RM-HNSCC and alters immune cells to potentially prime tumor response and reverse resistance to PD-1 inhibitors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In a single-arm phase 2 trial, patients with PD-1 inhibitor-refractory RM-HNSCC received <i>nab-</i>paclitaxel and nivolumab given in 28-day cycles. The primary endpoint was objective response rate (ORR), using RECIST1.1. Key secondary endpoints were duration of response (DoR), progression-free survival (PFS), and overall survival (OS). At least one tumor response assessment was required to be evaluable for ORR and PFS. A Simon optimal two-stage design tested the primary hypothesis (ORR: H<sub>1</sub> ≥ 50 vs. H<sub>0</sub> ≤ 30%, type I error 0.05; power 0.80). H<sub>0</sub> was rejected if ≥ 19 responses were observed in 46 patients. This sample size had a power of 80% to detect the difference in the key secondary hypothesis (median PFS: H<sub>1</sub> 6.0 vs. H<sub>0</sub> 3.6 months, two-sided, one-sample log rank test; type I error 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>From 9/28/2021–1/4/2024, 46 patients enrolled into the trial. One patient was not evaluable for ORR and PFS. Tumor response occurred in 21 of 45 evaluable patients (ORR 46.7%, 95% CI: 33.8–59.9; vs. H<sub>0</sub>, <i>p</i> = 0.0073) and included confirmed response in 20 and unconfirmed response in 1. The best tumor response was complete (4), partial (17), stable (18), and progression (6). The median DoR was 6.1 months (95% CI: 2.8–9.4). With a median follow-up of 14.1 months (IQR: 7.6–20.1), the median PFS was 5.5 months (95% CI: 3.9–7.8) and the median OS was 13.9 months (95% CI: 9.0–18.9). Treatment-related deaths did not occur.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Among patients with PD-1 inhibitor-refractory RM-HNSCC, <i>nab</i>-paclitaxel and nivolumab resulted in an ORR and median PFS that were better than historically reported with standard therapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>Trial registered on www.clinical","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12791152/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145950840","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}
<div> <section> <h3> Background</h3> <p>Prostate cancer (PCa) is a major cause of cancer-associated death in men. A crucial factor in its development and treatment resistance is tumor hypoxia, which drives metabolic reprogramming (especially reconfiguration towards glycolysis), mediated to a great extent by hypoxia-inducible factor-“HIF-1 alpha” (HIF-1a).</p> </section> <section> <h3> Aims</h3> <p>The present review summarizes (i) the mechanisms underlying hypoxia-induced glycolysis that enhances the aggressiveness of and treatment failure in PCa and (ii) recent developments in the field of theranostic nanoparticles (TNPs) with dual actions of inhibiting HIF-1a and downstream metabolic targets, while facilitating the imaging and treatment of the tumor.</p> </section> <section> <h3> Materials and Methods</h3> <p>We summarize available evidence for the hypoxia-glycolysis signaling in PCa and assess nanotechnology achievable theranostic approaches (i.e., liposomal-, polymer- and metallic nanoplatforms) to promote drug delivery, real-time tumor picture and modulation of hypoxic tumor microenvironments.</p> </section> <section> <h3> Results</h3> <p>Hypoxia-inducible factor-1 alpha (HIF-1a) driven hypoxia is a common phenotypic feature that underlies the increased glycolysis and aggressive tumor phenotype. TNPs have been developed with the aim of (a) enhancing the drug bioavailability, (b) enabling the selectivity of tumor and imaging, and (c) reducing the hypoxia-linked metabolic pathways. The use of PCa as a model for TNP development is especially timely as hypoxia crosses the intersection of androgen receptor (AR) signaling heavens (hormone therapy resistance) leading to progression to castration-resistant PCa (CRPC) and as the Prostate-Specific Membrane Antigen (PSMA) is greatly overexpressed and is a validated target for custom imaging and treatment.</p> </section> <section> <h3> Discussion</h3> <p>Compared with other hypoxia mediated solid tumors, hypoxia AR axis and PSMA overexpression have unique biological leverage for precision theranostics in PCa. Nevertheless, translation is limited by the issues of biocompatibility, complexities resulting from systematic regulations and constraints of scale-up manufacturing.</p> </section> <section> <h3> Conclusion</h3> <p>TNPs are a promising platform to integrate diagnosis and treatment of PCa as they inco
{"title":"Theranostic Nanoparticles in Prostate Cancer: Disrupting Hypoxia-Induced Glycolysis by Targeting Hypoxia-Inducible Factor-1 Alpha and Downstream Metabolites","authors":"Daniel Ejim Uti, Wilson Achu Omang, Esther Ugo Alum, Inalegwu Bawa, Okechukwu Paul-Chima Ugwu, Ayodeji Oluwafemi Idowu, Item Justin Atangwho, Godwin Eneji Egbung","doi":"10.1002/cam4.71519","DOIUrl":"10.1002/cam4.71519","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Prostate cancer (PCa) is a major cause of cancer-associated death in men. A crucial factor in its development and treatment resistance is tumor hypoxia, which drives metabolic reprogramming (especially reconfiguration towards glycolysis), mediated to a great extent by hypoxia-inducible factor-“HIF-1 alpha” (HIF-1a).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>The present review summarizes (i) the mechanisms underlying hypoxia-induced glycolysis that enhances the aggressiveness of and treatment failure in PCa and (ii) recent developments in the field of theranostic nanoparticles (TNPs) with dual actions of inhibiting HIF-1a and downstream metabolic targets, while facilitating the imaging and treatment of the tumor.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>We summarize available evidence for the hypoxia-glycolysis signaling in PCa and assess nanotechnology achievable theranostic approaches (i.e., liposomal-, polymer- and metallic nanoplatforms) to promote drug delivery, real-time tumor picture and modulation of hypoxic tumor microenvironments.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Hypoxia-inducible factor-1 alpha (HIF-1a) driven hypoxia is a common phenotypic feature that underlies the increased glycolysis and aggressive tumor phenotype. TNPs have been developed with the aim of (a) enhancing the drug bioavailability, (b) enabling the selectivity of tumor and imaging, and (c) reducing the hypoxia-linked metabolic pathways. The use of PCa as a model for TNP development is especially timely as hypoxia crosses the intersection of androgen receptor (AR) signaling heavens (hormone therapy resistance) leading to progression to castration-resistant PCa (CRPC) and as the Prostate-Specific Membrane Antigen (PSMA) is greatly overexpressed and is a validated target for custom imaging and treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>Compared with other hypoxia mediated solid tumors, hypoxia AR axis and PSMA overexpression have unique biological leverage for precision theranostics in PCa. Nevertheless, translation is limited by the issues of biocompatibility, complexities resulting from systematic regulations and constraints of scale-up manufacturing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>TNPs are a promising platform to integrate diagnosis and treatment of PCa as they inco","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12790959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145950868","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}
Amelie L. Salomon, Roland A. Ammann, Catherine Aftandilian, Konrad Bochennek, Eva Brack, Lee Dupuis, Caitlin W. Elgarten, Adam Esbenshade, Gabrielle M. Haeusler, Mia Karamatsu, Mette B. Moenster, Bob Phillips, Emily Schaeffer, Lillian Sung, Athanasios Tragiannidis, Nadja H. Vissing, Christa Koenig
Purpose
Fever in neutropenia (FN) is a potentially lethal complication of chemotherapy for cancer. Prompt administration of broad-spectrum antibiotics is standard of care. Despite conflicting results on the association of time to antibiotics (TTA) with outcomes, TTA limits are used as FN quality measure both in adult and pediatric oncology. This individual patient data (IPD) meta-analysis studied the association between TTA and outcomes in pediatric patients with FN.
Patients and Methods
IPD on TTA in pediatric patients with FN receiving chemotherapy for any malignancy was collected internationally. Three-level mixed binomial logistic regression analyzed the association of TTA with safety relevant events (SRE; death, admission to intensive care unit [ICU], bacteremia), primarily in patients with severe disease at presentation and secondarily in all patients.
Results
Data on 4006 FN episodes in 2073 patients, diagnosed 2016–2023, were reported from 15 study sites in eight countries. Median TTA was 61 min overall and 53 min in the 345 (8.6%) episodes with severe disease at presentation. Among these with severe disease, an SRE was reported in 119 (34%) episodes. Longer TTA (> 60 vs. ≤ 60 min) was associated with less SRE (odds ratio, 0.41; 95% CI, 0.24–0.70). This primary finding was confirmed in secondary and additional exploratory analyses.
Conclusion
This large, international and adequately powered IPD meta-analysis found no association between shorter TTA and improved clinical outcomes in pediatric patients with FN. This finding was consistent across analyses. These results challenge the continued use of TTA limits as a quality measure for pediatric oncology centers.
{"title":"Association of Time to Antibiotics With Outcome in Pediatric Patients Receiving Chemotherapy for Cancer With Fever in Neutropenia—An International Individual Patient Data Meta-Analysis","authors":"Amelie L. Salomon, Roland A. Ammann, Catherine Aftandilian, Konrad Bochennek, Eva Brack, Lee Dupuis, Caitlin W. Elgarten, Adam Esbenshade, Gabrielle M. Haeusler, Mia Karamatsu, Mette B. Moenster, Bob Phillips, Emily Schaeffer, Lillian Sung, Athanasios Tragiannidis, Nadja H. Vissing, Christa Koenig","doi":"10.1002/cam4.71512","DOIUrl":"10.1002/cam4.71512","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>Fever in neutropenia (FN) is a potentially lethal complication of chemotherapy for cancer. Prompt administration of broad-spectrum antibiotics is standard of care. Despite conflicting results on the association of time to antibiotics (TTA) with outcomes, TTA limits are used as FN quality measure both in adult and pediatric oncology. This individual patient data (IPD) meta-analysis studied the association between TTA and outcomes in pediatric patients with FN.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Patients and Methods</h3>\u0000 \u0000 <p>IPD on TTA in pediatric patients with FN receiving chemotherapy for any malignancy was collected internationally. Three-level mixed binomial logistic regression analyzed the association of TTA with safety relevant events (SRE; death, admission to intensive care unit [ICU], bacteremia), primarily in patients with severe disease at presentation and secondarily in all patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Data on 4006 FN episodes in 2073 patients, diagnosed 2016–2023, were reported from 15 study sites in eight countries. Median TTA was 61 min overall and 53 min in the 345 (8.6%) episodes with severe disease at presentation. Among these with severe disease, an SRE was reported in 119 (34%) episodes. Longer TTA (> 60 vs. ≤ 60 min) was associated with less SRE (odds ratio, 0.41; 95% CI, 0.24–0.70). This primary finding was confirmed in secondary and additional exploratory analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This large, international and adequately powered IPD meta-analysis found no association between shorter TTA and improved clinical outcomes in pediatric patients with FN. This finding was consistent across analyses. These results challenge the continued use of TTA limits as a quality measure for pediatric oncology centers.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12790953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145950896","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}
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