Translational cancer research最新文献

{"title":"Landscape and prognostic significance of oncogene drivers in metastatic castration sensitive prostate cancer.","authors":"Theodore Wang, Jongmyung Kim, Ritesh Kumar, Rebecca A Deek, Ryan Stephenson, Tina Mayer, Biren Saraiya, Saum Ghodoussipour, Thomas Jang, David Golombos, Vignesh Packiam, Ronald Ennis, Lara Hathout, Salma K Jabbour, Ozan Guler, Cem Onal, Matthew P Deek","doi":"10.21037/tcr-24-123","DOIUrl":"10.21037/tcr-24-123","url":null,"abstract":"<p><strong>Background: </strong>Tumor suppressors are well known drivers of cancer invasion and metastasis in metastatic castration sensitive prostate cancer (mCSPC). However, oncogenes are also known to be altered in this state, however the frequency and prognosis of these alterations are unclear. Thus, we aimed to study the spectrum of oncogene mutations in mCSPC and study the significance of these alteration on outcomes.</p><p><strong>Methods: </strong>Four hundred and seventy-seven patients with mCSPC were included who underwent next generation sequencing. Oncogene alterations were defined as mutations in <i>ALK, AKT1-3, BRAF, CCND1-3, CTNNB1, EGFR, ERBB2, FGFR1, FGFR2, HRAS, KRAS, MDM2, MET, MITF, MYC, NOTCH1-3, NRAS, PIK3CA, PI3KCB, PIK3R1, RET.</i> Endpoints of interests were radiographic progression-free survival (rPFS), time to development of CRPC (tdCRPC), and overall survival (OS). Kaplan Meier analysis was performed and Cox regression hazard ratios (HR) calculated.</p><p><strong>Results: </strong>A total of 477 patients were included with baseline characteristics with 117 patients (24.5%) harbored a mutation within an oncogene. A total of 172 oncogene mutations were found within the population with the most common being <i>MYC</i> (n=29; 16.9%), <i>PIK3CA</i> (n=24; 14%), <i>CTNNB1</i> (n=22, 12.8%), <i>BRAF</i> (n=10, 5.8%), and <i>CCND1</i> (n=10, 5.8%). Oncogene mutations were associated with inferior rPFS (19.2 <i>vs.</i> 32.2 months, P=0.03), tdCRPC (15.7 <i>vs.</i> 32.4 months, P<0.001), and OS (5-year OS 75.3% <i>vs.</i> 55.4%, P=0.01). On multivariable analysis oncogene mutations were strongly associated with tdCRPC (HR 1.42, P=0.03).</p><p><strong>Conclusions: </strong>Oncogenes are frequency mutated in mCSPC and associated with aggressive features and inferior outcomes. Future work will need to validate these results to better assess its significance in allowing for personalization of care.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 11","pages":"6235-6245"},"PeriodicalIF":1.5,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11651787/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-clear cell renal cell carcinoma narrative review: where we are in 2024.","authors":"Michael J Pierro, Alexander Gallan, Deepak Kilari","doi":"10.21037/tcr-24-737","DOIUrl":"10.21037/tcr-24-737","url":null,"abstract":"<p><strong>Background and objective: </strong>Advances in non-clear cell renal cell carcinoma (RCC) have lagged behind clear cell RCC due to the heterogeneity and relative rarity of the disease. However, more advanced molecular and genetic testing has allowed us to gain a more detailed and nuanced appreciation of these malignancies. This has laid the foundation for the identification of the distinct mutational and molecular patterns such as succinate dehydrogenase (SDH)-deficient RCC, fumarate hydratase (FH)-deficient RCC, and translocation RCC, so that clinicians can create a more personalized approach to their clinical management. Particularly for the rare non-papillary RCC variant histologies, clinical trial representation is lacking. In the discussed studies, no histology enrolled more than 29 patients of any particular RCC aside from Papillary. As such, evidence-based management decisions can be challenging to make for this patient population.</p><p><strong>Methods: </strong>We have collected the most up-to-date available evidence to describe the pathophysiology, molecular, and pathologic characteristics of the more commonly seen non-clear cell RCC variants, including papillary, chromophobe, translocation, FH-deficient, as well as a group of \"unclassified\" RCCs. Additionally, we provide an overview of the available evidence from recent clinical trials for non-clear cell RCC and current treatment paradigms.</p><p><strong>Key content and findings: </strong>The diagnostic approach for renal malignancies is rapidly changing, favoring a more molecular and genetically based approach. These techniques will allow for a more detailed understanding of the clinical behavior of these cancers. Most data for non-clear cell RCC are from single-arm phase 2 clinical trials. The clinical response to vascular endothelial growth factor (VEGF)-tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) varies greatly by histology.</p><p><strong>Conclusions: </strong>Molecularly targeted therapy as monotherapy or when combined with immunotherapy have efficacy in non-clear cell RCC, though there are differences in treatment response by histology.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 11","pages":"6403-6412"},"PeriodicalIF":1.5,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11651800/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of postoperative radiotherapy and definitive radiotherapy for non-metastatic adenoid cystic carcinoma of the head and neck, a propensity score matching based on the SEER database.","authors":"Mingyu Tan, Yanliang Chen, Tianqi Du, Qian Wang, Xun Wu, Xiaohu Wang, Hongtao Luo, Shilong Sun, Qiuning Zhang, Wenzhen Yuan","doi":"10.21037/tcr-24-1221","DOIUrl":"10.21037/tcr-24-1221","url":null,"abstract":"<p><strong>Background: </strong>Treating patients with head and neck adenoid cystic carcinoma (HNACC) presents surgical problems in various scenarios. Limited studies explore definitive radiation's impact on patient survival, with inadequate data correlating it to postoperative radiotherapy. Using the Surveillance, Epidemiology, and End Results (SEER) program, we conducted an objective analysis to evaluate the impact of definitive radiation on the survival of HNACC patients without distant metastases, aiming to uncover its nuanced pros and cons.</p><p><strong>Methods: </strong>This study conducted a comprehensive analysis of individuals diagnosed with HNACC within the SEER database from 2000 to 2023. Disease-specific survival (DSS) and overall survival (OS) were evaluated using diverse statistical methods. Propensity score matching (PSM) reduced covariate variations and selection biases, allowing for comparisons of postoperative and definitive radiotherapy groups.</p><p><strong>Results: </strong>A total of 2,072 patients were encompassed within this study. The postoperative radiotherapy group yielded significant advantages in OS and DSS (P<0.001). In matched cohorts, the 5-year prognostic OS stood at 55% and 37%, respectively, while DSS figures were 65% and 46%, correspondingly. In advanced T4 cases, DSS differences lacked significance (P=0.42). Additionally, the outcomes of OS and DSS were notably influenced by variables such as T-stage, N-stage, tumor stage, and chemotherapy.</p><p><strong>Conclusions: </strong>Surgical intervention remains a pivotal component of comprehensive treatment for patients diagnosed with operable HNACC. Definitive radiation is appropriate for less treatable situations, particularly in local advanced HNACC. Systemic treatment may assist HNACC patients at risk of distant metastases.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 11","pages":"6045-6056"},"PeriodicalIF":1.5,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11651770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-omics decipher the immune microenvironment and unveil therapeutic strategies for postoperative ovarian cancer patients.","authors":"Zhibing Liu, Fei Wang, Weiwei Chen, Yujie Zhai, Jinbo Jian, Xiaole Wang, Yingjiang Xu, Jiajia An, Lei Han","doi":"10.21037/tcr-24-656","DOIUrl":"10.21037/tcr-24-656","url":null,"abstract":"<p><strong>Background: </strong>Ovarian cancer (OC) is a highly aggressive and often fatal disease that frequently goes undetected until it has already metastasized. The classic treatment for OC involves surgery followed by chemotherapy. However, despite the effectiveness of surgery, relapse is still a common occurrence. Unfortunately, there is currently no ideal predictive model for the progression and drug sensitivity of postoperative OC patients. Cell death patterns play an important role in tumor progression. So we aimed to investigate their potential to be used as indicators of postoperative OC prognosis and drug sensitivity.</p><p><strong>Methods: </strong>A total of 12 programmed cell death (PCD) patterns were employed to construct novel classification and prognosis model. Bulk transcriptome, genomics, and clinical information were collected from The Cancer Genome Atlas (TCGA) Program-OV, GSE9891, GSE26712, GSE49997 and GSE63885. In addition, single-cell transcriptome data GSE210347 were procured from the Gene Expression Omnibus (GEO) database for subsequent analysis.</p><p><strong>Results: </strong>In this study, a novel PCD classification has been employed to phenotype postoperative OC patients, revealing that patients in cluster 1 exhibited heightened sensitivity to immune-based therapies combined with high expression of chemokines, interleukins, interferons, and checkpoints. Meanwhile, a programmed cell death index (PCDI) was established using an 8-gene signature with the help of a machine learning algorithm. The patients with high-PCDI had a worse prognosis after surgery in OC. In addition, we also found that patients with low PCDI patients may exhibit sensitivity to immunotherapy, while those with high PCDI patients may display increased responsiveness to tyrosine kinase inhibitors.</p><p><strong>Conclusions: </strong>This study provides a novel PCD model and nomogram that can effectively predict the clinical prognosis and drug sensitivity of OC patients post-surgery.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 11","pages":"6028-6044"},"PeriodicalIF":1.5,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11651737/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A lncRNA signature associated with endoplasmic reticulum stress supports prognostication and prediction of drug resistance in acute myelogenous leukemia.","authors":"Yu Fu, Shupeng Wang, Lingyu Meng, Yahui Liu","doi":"10.21037/tcr-24-722","DOIUrl":"10.21037/tcr-24-722","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Acute myelogenous leukemia (AML) is a type of blood cancer that is characterized by the accumulation of young and undeveloped myeloid cells in the bone marrow. It is considered a heterogeneous disease due to its diverse nature. Endoplasmic reticulum (ER) stress has emerged as a critical regulator of tumor development and drug resistance in various cancers. Long non-coding RNAs (lncRNAs) have been found to play a role in the development and prognosis of AML. Nonetheless, there is still limited understanding regarding the involvement of ER stress-related lncRNAs in AML prognosis and their predictive ability for drug resistance. The objective of this study was to examine the potential prognostic and predictive significance of an ER stress-related lncRNA signature in patients diagnosed with AML.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Based on the bulk RNA sequence data, we constructed an ER stress-related lncRNA signature using least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression analysis. We established nomograms and calibration curves to assess the clinical value of the signature by analyzing overall survival (OS) rates between different risk groups. We also conducted tumor mutation burden (TMB) analysis, predicted immune responses, performed functional and biological enrichment analysis, and evaluated drug sensitivity to investigate the impact of the prognostic signature. Additionally, we built a consensus cluster to explore the need for personalized immunotherapy approaches in treating patients with AML.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A prognostic signature was constructed using 227 ER stress-related lncRNAs that showed differential expression. Patients in the high-risk category demonstrated decreased OS rates in comparison to individuals in the low-risk category. The findings from the nomogram and receiver operating characteristic (ROC) curve analysis suggest a notable disparity in age between the different categories. Among the group at high risk, we noticed a considerably greater TMB in comparison to the low-risk group. Furthermore, individuals with both an elevated risk score and high TMB demonstrated the most unfavorable survival rates. Significant differences were observed in the immune responses between the groups classified as high- and low-risk. We then systematically evaluated three different clusters to assess immune responses and drug responses. Through analyzing the association between the risk score and various medications, we have discovered 18 potential drug contenders capable of effectively addressing AML. Furthermore, we conducted pathway analyses to determine the targeted pathways of these drugs.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Our data serve as a valuable resource for decoding the immune responses, somatic mutational landscape, drug resistance, and potential biological functions in AML patients. Additionally, our findings offer valuable insights into the ass","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 11","pages":"6165-6181"},"PeriodicalIF":1.5,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11651774/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Determining new disulfidptosis-associated lncRNA signatures pertinent to breast cancer prognosis and immunological microenvironment.","authors":"Yifan Zheng, Yufeng Lin, Yongcheng Zhang, Shangjie Liu, Yongxia Yang, Wenbin Huang","doi":"10.21037/tcr-24-513","DOIUrl":"10.21037/tcr-24-513","url":null,"abstract":"<p><strong>Background: </strong>Disulfidptosis is a novel form of cell death triggered by disulfide stress that may have important implications for breast cancer (BC) pathogenesis. Nevertheless, studies identifying disulfidptosis-associated long non-coding RNAs (lncRNAs) in BC have not been reported. This study aimed to investigate the prognostic potential of disulfidptosis-related lncRNAs in BC.</p><p><strong>Methods: </strong>RNA-sequencing data and clinical information of BC patients were obtained from The Cancer Genome Atlas (TCGA) database. The lncRNAs associated with disulfidptosis were identified through co-expression analysis. Subsequently, a risk signature consisting of 10 lncRNAs was constructed using univariate Cox and least absolute shrinkage and selection operator (LASSO) analyses, and its predictive power was validated.</p><p><strong>Results: </strong>The risk signature was found to be an independent prognostic factor for BC patients. Notably, the two subgroups defined by the risk signature exhibited different mutant gene profiles, and risk scores were significantly correlated with tumor mutation burden (TMB). Additionally, single-sample gene set enrichment analysis (ssGSEA) and immune checkpoint analyses indicated that the predicted trait was significantly associated with the immune status of BC patients. Furthermore, 55 potential anticancer drugs were identified that were associated with the signature.</p><p><strong>Conclusions: </strong>In this study, we successfully developed a prognostic model based on disulfidptosis-related lncRNAs, which enhances the accuracy of predicting the prognosis of BC patients. This model also offers a potential target and theoretical foundation for BC treatment, laying a robust groundwork for future research on the functional roles of disulfidptosis-associated lncRNAs in BC.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 11","pages":"5815-5829"},"PeriodicalIF":1.5,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11651735/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>CTNND2</i> gene expression in melanoma tissues and its effects on the malignant biological functions of melanoma cells.","authors":"Jiaojiao Qu, Xianfeng Cheng, Mingyan Liu, Qiang Zhang","doi":"10.21037/tcr-24-2159","DOIUrl":"10.21037/tcr-24-2159","url":null,"abstract":"<p><strong>Background: </strong>The catenin delta 2 (<i>CTNND2</i>) gene has been implicated in the progression of various cancers, but its specific role in melanoma has not yet been thoroughly investigated. This study sought to explore the expression and biological function of <i>CTNND2</i> in malignant melanoma tissues to identify new targets or biomarkers for melanoma diagnosis and treatment.</p><p><strong>Methods: </strong>Immunohistochemistry was used to examine the levels of <i>CTNND2</i> in melanoma and adjacent non-tumor tissues. A Western blot analysis was performed to quantify the expression levels of <i>CTNND2</i> in human immortalized keratinocytes and melanoma cell lines. The Cell Counting Kit-8 (CCK-8) assay, plate colony formation assay, cell adhesion assay, scratch test, and Transwell assay were used to assess the effects of <i>CTNND2</i> knockdown on the proliferation, adhesion, migration, and invasion of melanoma cells. The Harmonizome database was used to research the biological processes (BPs) involved in <i>CTNND2</i>.</p><p><strong>Results: </strong>In the melanoma tissues, <i>CTNND2</i> expression was substantially upregulated and its levels were closely linked with the pathological features of patients. The <i>CTNND2</i> levels were notably more increased in the melanoma cell lines than the immortalized keratinocytes. The suppression of the <i>CTNND2</i> gene substantially impeded the capacity of the melanoma cells to proliferate, migrate, and invade, and also significantly decreased their potential to attach to collagen I and IV, and fibronectin. The Harmonizome database results revealed a strong correlation between the BPs controlled by <i>CTNND2</i> and the focal adhesion signaling pathway of the cells. The inhibition of the <i>CTNND2</i> gene in melanoma cells resulted in a significant decrease in the phosphorylation of focal adhesion kinase (FAK) and the production of paxillin protein. In the melanoma cells, the reduction of <i>CTNND2</i> did not have a significant effect on the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. However, it did considerably prevent the activation of mitogen-activated extracellular signal-regulated kinase 1/2 (MEK1/2) and its downstream molecule extracellular signal-regulated protein kinase 1/2 (ERK1/2).</p><p><strong>Conclusions: </strong>The expression of the <i>CTNND2</i> gene is increased in melanoma tissues, which enhances the ability of melanoma cells to proliferate both <i>in vivo</i> and <i>in vitro</i>. Additionally, the <i>CTNND2</i> gene is crucial in controlling the adhesion process of melanoma cells. This mechanism is associated with the regulation of the FAK and MEK1/2/ERK1/2 signaling pathways. Based on our findings, <i>CTNND2</i> could be used as an oncogene target for melanoma and a new treatment target or diagnostic biomarker.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 11","pages":"6347-6363"},"PeriodicalIF":1.5,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11651744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroepithelial cell transforming 1 as a key regulator in non-small cell lung cancer: unveiling causal links and therapeutic potentials.","authors":"Xiaoqing Shangguan, Xinping Zhang, Xiwu Chen, Zheng Zhang, Lei Wang","doi":"10.21037/tcr-24-587","DOIUrl":"10.21037/tcr-24-587","url":null,"abstract":"<p><strong>Background: </strong>High incidence and mortality rates underscore lung cancer as a significant global health issue. Understanding the molecular mechanisms driving its progression is crucial for developing effective treatments. This study explores a potential molecular regulator that may contribute to the progression of non-small cell lung cancer (NSCLC) by utilizing bioinformatics analyses and laboratory experiments, aiming to provide insights that could inform future therapeutic strategies.</p><p><strong>Methods: </strong>Our research combined single-cell RNA sequencing (scRNA-seq) data analysis with the Mendelian randomization (MR) algorithm. MR analysis using genetic variants associated with NSCLC risk aimed to uncover causal relationships between genes and cancer traits. To validate the impact of neuroepithelial cell transforming 1 (<i>NET1</i>) on cellular proliferation and its role in inhibiting ferroptosis, we utilized quantitative real-time polymerase chain reaction (qRT-PCR), cell viability assays, and malondialdehyde (MDA) detection. Furthermore, molecular docking analyses of four compounds demonstrated their potential in modulating the downregulation of <i>NET1</i>.</p><p><strong>Results: </strong>ScRNA-seq exposed cellular diversity in non-malignant lungs and tumors. Distinct expression patterns in epithelial cells and identified gene pathways pointed to cell proliferation. <i>NET1</i>, causally linked to NSCLC through MR analysis, showed increased expression in tumors and correlated with unfavorable overall survival, validated by functional assays. Utilizing cell viability assays and MDA detection, our results validated the pivotal role of <i>NET1</i> in enhancing cellular proliferation and its efficacy in inhibiting ferroptosis. Doxorubicin, piroxicam, and quercetin emerged as potential drug candidates for NSCLC treatment based on molecular docking analysis.</p><p><strong>Conclusions: </strong>Our findings confirm <i>NET1</i>'s significant role in NSCLC progression, influencing cell proliferation, ferroptosis, immune activity regulation and identify potential therapeutics for targeted lung cancer treatment.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 11","pages":"6087-6104"},"PeriodicalIF":1.5,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11651745/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bladder sparing management for muscle-invasive bladder cancer after a complete clinical response: ready for prime time?-a narrative review.","authors":"Mann Patel, Kyle Moore, Benjamin L Lichtbroun, Ryan D Stephenson, Tina Mayer, Biren Saraiya, David Golombos, Thomas Jang, Vignesh T Packiam, Saum Ghodoussipour","doi":"10.21037/tcr-24-726","DOIUrl":"10.21037/tcr-24-726","url":null,"abstract":"<p><strong>Background and objective: </strong>A standard of care for muscle-invasive bladder cancer (MIBC) is cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC). Given recent improvements in NAC and the morbidity associated with RC, bladder-sparing therapy has been investigated as a promising treatment for patients with MIBC who experience a complete clinical response (CCR) to systemic therapy. However, clinical staging is unreliable, making it challenging to determine ideal candidates for bladder-sparing therapy. Our primary objective is to review the efficacy of NAC, strategies for determining a CCR as a surrogate for a complete pathologic response, and the emerging role of imaging, tumor genomics, and biomarkers in selecting candidates for bladder-sparing therapy.</p><p><strong>Methods: </strong>We surveyed the literature for studies investigating the outcomes of current treatment modalities for MIBC and methods for determining a CCR following systemic therapy as well as the impact this has on pathologic staging. Studies employing imaging, tumor biomarkers, and genomics were included.</p><p><strong>Key content and findings: </strong>Clinical staging with cystoscopy or transurethral resection shows significant discordance with final pathology, with high rates of understaging. Multiparametric magnetic resonance imaging (mpMRI) has shown strong utility in determining the presence of MIBC, but it has yet to reliably identify CCR. Meanwhile, somatic DNA damage repair mutations and biomarkers such as circulating and urinary tumor DNA are strong predictors of recurrence, showing promise in predicting and monitoring a CCR to systemic therapy. Multiple ongoing trials are currently assessing the use of biomarkers and genomic analyses in determining eligibility for bladder-sparing therapy.</p><p><strong>Conclusions: </strong>While no one method has reliably demonstrated the ability to detect a true CCR, a multimodal approach involving imaging, biomarkers, and genomic analyses holds promise. We eagerly await the results of clinical trials investigating these tools, which may allow for the safe recommendation of bladder-sparing therapy.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 11","pages":"6413-6429"},"PeriodicalIF":1.5,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11651806/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A narrative clinical trials review in the realm of focal therapy for localized prostate cancer.","authors":"Alon Lazarovich, Vijay Viswanath, Aaron S Dahmen, Abhinav Sidana","doi":"10.21037/tcr-23-2406","DOIUrl":"10.21037/tcr-23-2406","url":null,"abstract":"<p><strong>Background and objective: </strong>The role of focal therapy in the treatment of localized prostate cancer is evolving. However, despite accumulating evidence, current guidelines and regulatory bodies refrain from endorsing focal therapy outside of clinical trials. Our goal was the to review the focal therapy realm for ongoing clinical trials and high impact recently published trials.</p><p><strong>Methods: </strong>Our comprehensive investigation includes an exhaustive review of ClinicalTrials.gov and PubMed databases, identifying and analyzing clinical trials with diverse modalities of focal therapy. In this review, we focused on critical ongoing and recently concluded clinical trials (2-15-2023) in the focal therapy realm.</p><p><strong>Key content and findings: </strong>We identified several trials on focal therapy at various stages of progression and various trial design. The trials study all different modalities of focal therapy including high-intensity focused ultrasound (HIFU), cryoablation, irreversible electroporation (IRE), focal laser ablation (FLA), transurethral ultrasound ablation (TULSA)-PRO^®, and Water Vapor ablation. The trials focus both on oncological outcomes and quality of life outcomes. Novel clinical trials study the additive impact of androgen deprivation therapy (ADT) to different focal therapy modalities.</p><p><strong>Conclusions: </strong>The exploration of focal therapy in prostate cancer holds promise for achieving oncological control while minimizing the impact on patients' quality of life. Continued research and trial results will play a pivotal role in delineating focal therapy's optimal role in the broader prostate cancer treatment spectrum.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 11","pages":"6529-6539"},"PeriodicalIF":1.5,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11651783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}