Cancer Innovation最新文献

{"title":"SKIL Promotes Pancreatic Cancer Metastasis by Inhibiting TSPYL2 to Activate the TGF-β Pathway","authors":"Chenxi Wang,&nbsp;Weiwei Song,&nbsp;Yixuan Zhang,&nbsp;Hongming Deng,&nbsp;Zixiang Zhou,&nbsp;Jing Zhu,&nbsp;Xiaobing Wang","doi":"10.1002/cai2.70011","DOIUrl":"https://doi.org/10.1002/cai2.70011","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Pancreatic adenocarcinoma (PAAD) represents a highly fatal form of cancer. The 5-year survival rate for patients with this disease is only around 10%. A significant hurdle in its management is the absence of characteristic early-stage symptoms. As a result, a large majority of pancreatic cancer patients are diagnosed when the disease has reached an advanced stage or has metastasized. Consequently, taking measures to suppress the occurrence of metastasis in pancreatic cancer can bring about a substantial improvement in patients' survival rates and overall prognosis. <i>SKIL</i>, known to promote cancer progression, is implicated in cell proliferation, epithelial–mesenchymal transition (EMT), and metastasis, but its specific function in pancreatic cancer remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We investigated the effects of <i>SKIL</i> on the proliferation, apoptosis, and metastasis of pancreatic cancer cells. Through ChIP-seq, we identified the <i>SKIL</i> downstream target gene and further explored the mechanism by which <i>SKIL</i> regulates the metastasis of pancreatic cancer cells through functional experiments and Western blot.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A high level of <i>SKIL</i> expression is associated with an unfavorable prognosis in PAAD; it promotes cell migration and EMT. Through ChIP-seq analysis, we identified that <i>SKIL</i> inhibits <i>TSPYL2</i>, a nuclear protein regulating the TGF-β pathway by binding to the <i>TGFB1</i> promoter. Further studies carried out by us confirmed that <i>SKIL</i> modulates the TGF-β pathway via <i>TSPYL2</i>, facilitating EMT and metastasis in pancreatic cancer cells, independent of Smad4.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings reveal a novel regulatory mechanism involving <i>SKIL</i>, <i>TSPYL2</i>, and the TGF-β pathway, offering new therapeutic targets for PAAD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":100212,"journal":{"name":"Cancer Innovation","volume":"4 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cai2.70011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085424","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":"Expert Consensus on the Clinical Application of PI3K/AKT/mTOR Inhibitors in the Treatment of Breast Cancer (2025 Edition)","authors":"The Breast Cancer Expert Committee of the National Quality Control Center for Cancer,&nbsp;The Expert Committee on Cancer Prevention and Treatment of the Health China Research Center,&nbsp;The Society of Clinical Research on Oncology Medications of the China Anti-Cancer Association,&nbsp;The Society of Onco-Pathology of the China Anti-Cancer Association","doi":"10.1002/cai2.70008","DOIUrl":"https://doi.org/10.1002/cai2.70008","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB or AKT)/mammalian target of rapamycin (mTOR) signaling pathway (PAM pathway) plays a critical role in breast cancer pathogenesis and progression, and is closely linked with resistance to endocrine therapy in advanced breast cancer. Randomized clinical trials have shown that PI3K/AKT/mTOR inhibitors deliver significant clinical benefits, particularly for patients with advanced hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In 2022, the Breast Cancer Expert Committee of the National Cancer Quality Control Center convened specialists in related fields to draft the “Expert Consensus on the Clinical Application of PI3K/AKT/mTOR Inhibitors in the Treatment of Advanced Breast Cancer.” This consensus raised awareness of these inhibitors among oncologists in China and improved the precision of clinical decision-making. In recent years, growing evidence has emphasized the importance of targeting the PAM pathway, reflected in the approval of several innovative agents. This consensus is an updated 2025 edition that retains the foundational structure of the 2022 edition while incorporating notable updates.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Updates to the consensus include the introduction of newly approved PAM pathway inhibitors, updated data from recent clinical trials, and expanded therapeutic applications. The revised guidance also offers updated recommendations for genetic testing to detect alterations in relevant pathways. The section on managing drug-related adverse events has been significantly expanded, providing detailed insights into different types of adverse events and their management. These updates aim to enhance the clinical application of PAM pathway inhibitors, promote precision medicine, and ultimately, improve survival outcomes for patients with breast cancer.</p>\u0000 </section>\u0000 </div>","PeriodicalId":100212,"journal":{"name":"Cancer Innovation","volume":"4 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cai2.70008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143809671","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":"Coexistent Pulmonary Tuberculosis and Lung Cancer: An Analysis of Incidence Trends, Financial Burdens and Influencing Factors","authors":"Fei Qi,&nbsp;Hongjie Yang,&nbsp;Yi Han,&nbsp;Yujie Dong,&nbsp;Fan Zhang,&nbsp;Yishuo Wang,&nbsp;Juan Du,&nbsp;Yuan Gao,&nbsp;Xueguang Hu,&nbsp;Liqun Zhang,&nbsp;Tongmei Zhang","doi":"10.1002/cai2.70009","DOIUrl":"https://doi.org/10.1002/cai2.70009","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Tuberculosis (TB) and lung cancer (LC) are both major global health threats. However, coexistent pulmonary TB and LC (TBLC) is a unique condition for which incidence trends and risk factors have not been fully defined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We retrospectively reviewed the medical records of patients with TBLC and LC alone between 2010 and 2022 at Beijing Chest Hospital, the standard authority for the diagnosis and treatment of TB and LC in China. The cumulative incidence rate (CIR) of TBLC was calculated as the number of new TBLC cases/number of LC cases at risk per 100,000 annually. The comparative incidence rate ratio (IRR) was estimated to be the TB incidence in LC patients/TB incidence in the general population. Logistic regression was used to explore risk factors for TBLC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The CIR of TBLC has rapidly increased each year since 2014 and reached 7027 per 100,000 LC patients in 2022. Patients with LC had a higher risk of developing active TB than the general population (IRR = 25.21, 95% confidence interval [CI]: 21.54–29.89). Medical expenditure per patient was 100.60 thousand yuan for those with TBLC and 105.60 thousand yuan for patients with LC (<i>p</i> = 0.687). Patients with TBLC were older (63.61 ± 10.46 vs. 61.08 ± 10.77, <i>p</i> &lt; 0.001) and had a higher male-to-female ratio (2.82 vs. 1.59, <i>p</i> = 0.044) than those with LC alone. A tendency of earlier disease onset was observed in patients with LC rather than TBLC. A majority (44.92%) of TBLC lesions were located in the upper lobes of the lung and had a higher proportion of squamous cell carcinomas than LC alone (32.24% vs. 27.49%, <i>p</i> = 0.002). TBLC also presented more aggressively, with more lymph node involvement and distant metastases. Multivariate analysis revealed that older age, the male sex, mediastinal lymph node invasion, lung/bone metastases, anemia, hypoalbuminemia, malnutrition, pulmonary fibrosis, and chronic obstructive pulmonary disease were risk factors for active TBLC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>There has been a rise in the incidence of coexistent TBLC and a concomitant increase in its financial burden in China that deserves more awareness and attention.</p>\u0000 </section>\u0000 </div>","PeriodicalId":100212,"journal":{"name":"Cancer Innovation","volume":"4 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cai2.70009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143786784","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":"Prognostic Effect of Neck Dissection and Risk Factors for Occult Lymph Node Metastasis in cN0 Parotid Carcinoma","authors":"Yudong Ning,&nbsp;Yixuan Song,&nbsp;Yuqin He,&nbsp;Han Li,&nbsp;Shaoyan Liu","doi":"10.1002/cai2.70007","DOIUrl":"https://doi.org/10.1002/cai2.70007","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aimed to explore the prognostic effect of neck dissection and to identify risk factors associated with occult lymph node metastasis (OLNM) in clinically node-negative (cN0) parotid carcinoma (PC).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A retrospective analysis was conducted on cN0 PC patients who underwent primary surgery at the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, between 2012 and 2022. Kaplan–Meier (KM) survival analyses were carried out to evaluate differences in progression-free survival (PFS) and overall survival (OS) between patients undergoing neck dissection and those who did not. Clinical variables associated with OLNM in the neck dissection group were assessed using univariate and multivariate logistic regression analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 472 PC patients, 133 were classified as cN0 following initial surgery, of whom 75 (56.4%) underwent neck dissection. Pathological lymph node metastases were confirmed in 20 (26.7%) patients in the neck dissection cohort. Poor tumor differentiation was identified as an independent risk factor for OLNM (<i>p</i> = 0.017). No significant differences in PFS or OS were observed between the no-neck dissection and neck dissection groups for patients with low-grade or well-differentiated tumors (<i>p</i> &gt; 0.05). However, neck dissection was associated with significantly prolonged PFS in patients with tumors of higher grade or low to moderate differentiation (<i>p</i> &lt; 0.05). Notably, OS did not improve with neck dissection across all subgroups (<i>p</i> &gt; 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Poorly differentiated tumors in cN0 PC are independently associated with a higher risk of OLNM. While prophylactic neck dissection may enhance PFS in patients with higher grade or poorly differentiated tumors, it does not confer a survival benefit in terms of OS. These findings support the selective use of neck dissection in patients with higher risk tumor profiles.</p>\u0000 </section>\u0000 </div>","PeriodicalId":100212,"journal":{"name":"Cancer Innovation","volume":"4 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cai2.70007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143786785","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":"A Survey of Clinical Practices for Hepatocellular Carcinoma Among Experts at Tertiary Hospitals in China From 2020 to 2021","authors":"Hong Zhao,&nbsp;Yilei Mao,&nbsp;Hongguang Wang,&nbsp;Aiping Zhou,&nbsp;Zhengqiang Yang,&nbsp;Yue Han,&nbsp;Gong Li,&nbsp;Xinyu Bi,&nbsp;Chunyi Hao,&nbsp;Xiaodong Wang,&nbsp;Jun Zhou,&nbsp;Chaoliu Dai,&nbsp;Feng Wen,&nbsp;Jingdong Zhang,&nbsp;Ruibao Liu,&nbsp;Tao Li,&nbsp;Lei Zhao,&nbsp;Zuoxing Niu,&nbsp;Tianfu Wen,&nbsp;Qiu Li,&nbsp;Hongmei Zhang,&nbsp;Xiaoming Chen,&nbsp;Minshan Chen,&nbsp;Ming Zhao,&nbsp;Yajin Chen,&nbsp;Jun Yu,&nbsp;Jie Shen,&nbsp;Xiangchen Li,&nbsp;Lianxin Liu,&nbsp;Zhiyong Huang,&nbsp;Wei Zhang,&nbsp;Feng Shen,&nbsp;Weiping Zhou,&nbsp;Zhengang Yuan,&nbsp;Jian Zhai,&nbsp;Ningling Ge,&nbsp;Yongjun Chen,&nbsp;Huichuan Sun,&nbsp;Jianqiang Cai","doi":"10.1002/cai2.70006","DOIUrl":"https://doi.org/10.1002/cai2.70006","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death in China. The rapid progress in systemic therapies has led to the approval of many therapeutic methods that have quickly changed clinical guidelines and practices. Because of the high heterogeneity of HCC, there are still some gaps between the guidelines and real-world clinical practice. The present study surveyed experts in China to investigate the current treatment concepts and clinical practice regarding HCC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A questionnaire survey on the treatment concepts and clinical practice of HCC was administered to 310 experts with senior professional titles in 2020 and 312 experts in 2021. The results were analyzed and compared.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>For treating patients with resectable HCC, 28% of hepatobiliary surgeons indicated neoadjuvant therapy, and 7% chose systemic therapy ± locoregional therapy as 1 L therapy in 2021 compared with 20% and 1% in 2020. More experts chose adjuvant treatment within 1 month in 2021 compared with 2020, and 6 months and 12 months were the leading choices for the duration of adjuvant treatment. In 2021, 79% of surgeons and 19% of interventionalists were willing to conduct downstaging/conversion therapy for patients with potentially resectable HCC, and 78% chose tyrosine kinase inhibitors (TKI) + immunotherapy (IO) + locoregional therapy for cases in which R0 resection could not be achieved. For completely unresectable HCC, more experts preferred TKI + IO-based therapy as 1 L therapy in 2021 compared with 2020 (78% vs. 55%). The proportion of experts who indicated TKI + IO-based therapy as 2 L therapy increased from 32% in 2020 to 40% in 2021.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The survey results indicated that in 2021, compared with 2020, more experts opted to administer IO + TKI for the treatment of liver cancer, and more experts and patients were willing to participate in clinical research.</p>\u0000 </section>\u0000 </div>","PeriodicalId":100212,"journal":{"name":"Cancer Innovation","volume":"4 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cai2.70006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143793709","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":"Guideline for the Management Pathway and Quality Control of Breast Cancer Prevention and Treatment in China's Counties","authors":"Breast Cancer Expert Committee of National Cancer Quality Control Center,&nbsp;Cancer Prevention and Treatment Committee of Healthy China Research Center","doi":"10.1002/cai2.70005","DOIUrl":"https://doi.org/10.1002/cai2.70005","url":null,"abstract":"<p>Breast cancer is one of the most common malignant tumors among women in China, with approximately 306,000 new cases reported in 2016. Notably, around 33% (100,400) of these cases occurred in rural areas. County-level hospitals, encompassing counties and county-level cities, serve as the primary diagnostic units for the majority of rural breast cancer patients. These hospitals are integral to cancer prevention, screening, maintenance treatment, rehabilitation, follow-up, and referral processes. However, economic and geographical constraints result in county-level hospitals being relatively deficient in medical equipment, health human resources, and drug accessibility. Consequently, there is a critical need for breast cancer prevention and management guidelines that are tailored to the specific conditions of China's counties. In response to this need, and within the policy framework of hierarchical diagnosis and treatment, a Chinese expert group has developed the <i>Guideline for the Management Pathway and Quality Control of Breast Cancer Prevention and Treatment in China's Counties (2023 Edition)</i>. This guideline aims to expand the availability of quality medical resources, ensure better distribution of these resources across regions, and enhance the capacity for breast cancer prevention and treatment. Ultimately, the goal is to improve the prognosis and quality of life for breast cancer patients in China's counties. This guideline includes clear and concise path diagrams that are easy to implement in clinical practice, serving as a valuable reference for clinicians in county-level hospitals.</p>","PeriodicalId":100212,"journal":{"name":"Cancer Innovation","volume":"4 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cai2.70005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707269","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":"Individualized Analysis of Nipple-Sparing Mastectomy Versus Modified Radical Mastectomy Using Deep Learning","authors":"Enzhao Zhu,&nbsp;Linmei Zhang,&nbsp;Pu Ai,&nbsp;Jiayi Wang,&nbsp;Chunyu Hu,&nbsp;Huiqing Pan,&nbsp;Weizhong Shi,&nbsp;Ziqin Xu,&nbsp;Yidan Fang,&nbsp;Zisheng Ai","doi":"10.1002/cai2.70002","DOIUrl":"https://doi.org/10.1002/cai2.70002","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>This study aimed to evaluate the impact of nipple-sparing mastectomy (NSM) and modified radical mastectomy (MRM) on individual survival outcomes and to assess the potential of neoadjuvant systemic therapy (NST) in reducing surgical intervention requirements.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To develop treatment recommendations for breast cancer patients, five machine learning models were trained. To mitigate bias in treatment allocation, advanced statistical methods, including propensity score matching (PSM) and inverse probability treatment weighting (IPTW), were applied.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>NSM demonstrated either superior or noninferior survival outcomes compared with MRM across all breast cancer stages, irrespective of adjustments for IPTW and PSM. Among all models and National Comprehensive Cancer Network guidelines, the Balanced Individual and Mixture Effect (BIME) for survival regression model proposed in this study showed the strongest protective effects in treatment recommendations, as evidenced by an IPTW hazard ratio of 0.39 (95% CI: 0.26–0.59), an IPTW risk difference of 19.66% (95% CI: 18.20–21.13), and an IPTW difference in restricted mean survival time of 17.77 months (95% CI: 16.37–19.21). NST independently reduced the probability of surgical intervention by 1.4% (95% CI: 0.9%–2.0%), with the greatest impact observed in patients with locally advanced breast cancer, in whom a 4.5% reduction (95% CI: 3.8%–5.2%) in surgical selection was noted.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The BIME model provides superior accuracy in recommending surgical approaches for breast cancer patients, leading to improved survival outcomes. These findings underscore the potential of BIME to enhance clinical decision-making. However, further investigation incorporating comprehensive prognostic evaluation is needed to optimize the surgical selection process and refine its clinical utility.</p>\u0000 </section>\u0000 </div>","PeriodicalId":100212,"journal":{"name":"Cancer Innovation","volume":"4 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cai2.70002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707270","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":"Investigating the Mechanism of IFN-γ-Inducible Lysosomal Thiol Reductase-Mediated Inhibition of Breast Cancer Cell Proliferation","authors":"Qin Liu,&nbsp;Xiaoning Yuan,&nbsp;Youcheng Shao,&nbsp;Xiaoqing Guan,&nbsp;Kaixiang Feng,&nbsp;Mengfei Chu,&nbsp;Le Chen,&nbsp;Hui Li,&nbsp;Hanhui Liu,&nbsp;Jingwei Zhang,&nbsp;Yihao Tian,&nbsp;Lei Wei","doi":"10.1002/cai2.161","DOIUrl":"https://doi.org/10.1002/cai2.161","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Breast cancer has become a severe threat to human health, making it imperative to identify effective drugs and therapeutic targets.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Various molecular biology experiments, such as western blot analysis, cytologic effect, co-immunoprecipitation, and immunofluorescence assays, as well as a nude mouse xenograft tumor model, were used to comprehensively analyze the impact of gamma-interferon-inducible lysosomal thiol reductase (GILT) on the malignant phenotype of breast cancer cells. This work was performed to examine GILT expression levels and explore the potential mechanism in breast cancer.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>GILT protein expression levels were significantly lower in breast cancer cells than in normal breast epithelial cells. Overexpressing GILT inhibited breast cancer cell proliferation and migration and slowed tumor growth. GILT inhibited the interaction between the MYC and WDR5 transcription complex and played a tumor-suppressive role. The MYC/WDR5 transcription complex inhibitor OICR-9429 could synergize with GILT to inhibit breast cancer cell proliferation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study reveals a potential mechanism by which GILT can slow breast cancer growth, as well as identifying the possible clinical application value of small molecule inhibitor OICR-9429. These data collectively provide novel treatment strategies for breast cancer therapy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":100212,"journal":{"name":"Cancer Innovation","volume":"4 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cai2.161","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143629865","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":"Inhibition of Putative Ibrutinib Targets Promotes Atrial Fibrillation, Conduction Blocks, and Proarrhythmic Electrocardiogram Indices: A Mendelian Randomization Analysis","authors":"Hongxuan Xu,&nbsp;Bingxun Li,&nbsp;Pinchao Lv,&nbsp;Ying Chen,&nbsp;Yanyun Lin,&nbsp;An Zhang,&nbsp;Jing Zhao,&nbsp;Guoxiong Zhou,&nbsp;Lin Wu","doi":"10.1002/cai2.70004","DOIUrl":"https://doi.org/10.1002/cai2.70004","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The mechanism by which ibrutinib, a Bruton's tyrosine kinase inhibitor, can elevate the risk of arrhythmias is not fully elucidated. In this study, we explored how inhibition of off-target kinases can contribute to this phenomenon.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed a Mendelian randomization analysis to examine the causal associations between genetically proxied inhibition of six putative ibrutinib drug targets (ErbB2/HER2, CSK, JAK3, TEC, BLK, and PLCG2) and the atrial fibrillation (AF) risk, proarrhythmic ECG indices, and cardiometabolic traits and diseases. Inverse-variance weighted random-effects models and Wald ratio were used to examine the associations between genetically proxied inhibition of these drug targets and the risk of outcomes. Colocalization analyses were employed to examine the robustness of the causally significant findings. ELISAs were used to measure ErbB2 levels in intracardiac plasma samples.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Genetically proxied ErbB2 inhibition was associated with an increased AF risk, higher P wave terminal force, and prolonged QTc interval. Patients with AF had significantly higher intracardiac ErbB2 levels compared with patients with paroxysmal supraventricular tachycardia. CSK inhibition prolonged the QRS duration, decreased the QTc interval, and was potentially linked to conduction blocks. PLCG2 inhibition led to decreased P wave terminal force, shorter QTc interval, and increased risk of left bundle branch block. BLK inhibition shortened the QTc interval and was also associated with atrioventricular block.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The off-target effects and downstream targets of ibrutinib, including CSK, PLCG2, ERBB2, TEC, and BLK, may lead to cardiac electrical homeostasis imbalances and lethal cardiovascular diseases. Using drugs that inhibit these targets should be given extra caution.</p>\u0000 </section>\u0000 </div>","PeriodicalId":100212,"journal":{"name":"Cancer Innovation","volume":"4 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cai2.70004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595502","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":"Computed Tomography-Based Habitat Analysis for Prognostic Stratification in Colorectal Liver Metastases","authors":"Chaoqun Zhou,&nbsp;Hao Xin,&nbsp;Lihua Qian,&nbsp;Yong Zhang,&nbsp;Jing Wang,&nbsp;Junpeng Luo","doi":"10.1002/cai2.70000","DOIUrl":"https://doi.org/10.1002/cai2.70000","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Colorectal liver metastasis (CRLM) has a poor prognosis, and traditional prognostic models have certain limitations in clinical application. This study aims to evaluate the prognostic value of CT-based habitat analysis in CRLM patients and compare it with existing traditional prognostic models to provide more evidence for individualized treatment of CRLM patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This retrospective study included 197 patients with CRLM whose preoperative contrast-enhanced CT images and corresponding DICOM Segmentation Objects (DSOs) were obtained from The Cancer Imaging Archive (TCIA). Tumor regions were segmented, and habitat features representing distinct subregions were extracted. An unsupervised K-means clustering algorithm classified the tumors into two clusters based on their habitat characteristics. Kaplan–Meier analysis was used to evaluate overall survival (OS), disease-free survival (DFS), and liver-specific DFS. The habitat model's predictive performance was compared with the Clinical Risk Score (CRS) and Tumor Burden Score (TBS) using the concordance index (C-index), Integrated Brier Score (IBS), and time-dependent area under the curve (AUC).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The habitat model identified two distinct patient clusters with significant differences in OS, DFS, and liver-specific DFS (<i>p</i> &lt; 0.01). Compared with CRS and TBS, the habitat model demonstrated superior predictive accuracy, particularly for DFS and liver-specific DFS, with higher time-dependent AUC values and improved model calibration (lower IBS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>CT-based habitat analysis captures spatial tumor heterogeneity and provides enhanced prognostic stratification in CRLM. The method outperforms conventional models and offers potential for more personalized treatment planning.</p>\u0000 </section>\u0000 </div>","PeriodicalId":100212,"journal":{"name":"Cancer Innovation","volume":"4 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cai2.70000","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595500","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}