Onco最新文献 - Book学术

A Transformative Technology Linking Patient’s mRNA Expression Profile to Anticancer Drug Efficacy 将患者 mRNA 表达谱与抗癌药物疗效联系起来的变革性技术

Onco Pub Date : 2024-07-14 DOI: 10.3390/onco4030012

Chen Yeh, Shu-Ti Lin, Hung-Chih Lai

{"title":"A Transformative Technology Linking Patient’s mRNA Expression Profile to Anticancer Drug Efficacy","authors":"Chen Yeh, Shu-Ti Lin, Hung-Chih Lai","doi":"10.3390/onco4030012","DOIUrl":"https://doi.org/10.3390/onco4030012","url":null,"abstract":"As precision medicine such as targeted therapy and immunotherapy often have limited accessibility, low response rate, and evolved resistance, it is urgent to develop simple, low-cost, and quick-turnaround personalized diagnostic technologies for drug response prediction with high sensitivity, speed, and accuracy. The major challenges of drug response prediction strategies employing digital database modeling are the scarcity of labeled clinical data, applicability only to a few classes of drugs, and losing the resolution at the individual patient level. Although these challenges have been partially addressed by large-scale cancer cell line datasets and more patient-relevant cell-based systems, the integration of different data types and data translation from pre-clinical to clinical utilities are still far-fetched. To overcome the current limitations of precision medicine with a clinically proven drug response prediction assay, we have developed an innovative and proprietary technology based on in vitro patient testing and in silico data analytics. First, a patient-derived gene expression signature was established via the transcriptomic profiling of cell-free mRNA (cfmRNA) from the patient’s blood. Second, a gene-to-drug data fusion and overlaying mechanism to transfer data were performed. Finally, a semi-supervised method was used for the database searching, matching, annotation, and ranking of drug efficacies from a pool of ~700 approved, investigational, or clinical trial drug candidates. A personalized drug response report can be delivered to inform clinical decisions within a week. The PGA (patient-derived gene expression-informed anticancer drug efficacy) test has significantly improved patient outcomes when compared to the treatment plans without PGA support. The implementation of PGA, which combines patient-unique cfmRNA fingerprints with drug mapping power, has the potential to identify treatment options when patients are no longer responding to therapy and when standard-of-care is exhausted.","PeriodicalId":74339,"journal":{"name":"Onco","volume":"43 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141650176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Revisiting the Role of PD-L1 Overexpression in Prognosis and Clinicopathological Features in Patients with Oral Squamous Cell Carcinoma 重新审视 PD-L1 过表达在口腔鳞状细胞癌患者预后和临床病理特征中的作用

Onco Pub Date : 2024-07-12 DOI: 10.3390/onco4030011

Fernando Leporace-Jiménez, Isabel Portillo-Hernandez, Justino Jiménez-Almonacid, Ignacio Zubillaga Rodriguez, María Mejía-Nieto, Pablo Caballero Pedrero, G. S. Aniceto

{"title":"Revisiting the Role of PD-L1 Overexpression in Prognosis and Clinicopathological Features in Patients with Oral Squamous Cell Carcinoma","authors":"Fernando Leporace-Jiménez, Isabel Portillo-Hernandez, Justino Jiménez-Almonacid, Ignacio Zubillaga Rodriguez, María Mejía-Nieto, Pablo Caballero Pedrero, G. S. Aniceto","doi":"10.3390/onco4030011","DOIUrl":"https://doi.org/10.3390/onco4030011","url":null,"abstract":"Background: PD1 and its ligand PD-L1 are related to prognosis in many solid tumors; however, their role in oral squamous cell carcinoma (OSCC) remains unclear. Methods: A retrospective monocentric study including all patients with OSCC diagnosed and treated between January 2020 and May 2022 was performed. PD-L1 expression was assessed per a combined positive score (CPS), considering a CPS of > or equal to 1 as positive (1–20 indicating “low expression” and ≥20 indicating “high”). A descriptive analysis of the patient cohort and tumors was performed, including tumor size, stage, lymph node involvement, recurrence, and survival. Results: In total, 65 patients (65 tumors) were analyzed. A total of 66.15% of the tumors were in advanced stages (III-IV), of which 97.67% expressed PD-L1+, compared with 71.42% in the early stages (I–II). T4 tumors expressed PD-L1 in 100% of cases, compared with 54% in T1 tumors. A total of 50.79% of the tumors showed lymph node involvement (pN+), with 100% of the pN+ showing PD-L1+. The prevalence of pN+ was 59.38% vs. 40.63% for high vs. low PD-L1 expression, respectively. Patients’ follow-ups ranged from 2 to 34.5 months. No significant difference was seen between overall survival (OS) and PD-L1 +/− (CPS ≥ 1 vs. CPS < 1) or high (CPS ≥ 20) and low (CPS < 20) PD-L1 expression (p < 0.97 and 0.64, respectively). Conclusions: The method used to measure PD-L1 (a laboratory test with Dako 22C3 anti-PD-L1 primary antibodies) was reliable and accurate, with a correlation coefficient between PD-L1 expression in the biopsy and the surgical piece of 0.83 (p < 0.0001). A CPS of ≥1 was observed in large tumors (p < 0.001) and was correlated with that of lymph node metastases (p < 0.004). Further analysis of PD-L1 expression in OSCC and studies to determine its relevance in tumor biology and prognosis is needed.","PeriodicalId":74339,"journal":{"name":"Onco","volume":"65 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141652512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The World of Immunotherapy Needs More Than PD-1/PD-L1—Two of the New Kids on the Block: LAG-3 and TIGIT 免疫疗法世界需要的不仅仅是 PD-1/PD-L1--两种新药：LAG-3和TIGIT

Onco Pub Date : 2024-07-01 DOI: 10.3390/onco4030010

J. Gama, Paulo Teixeira, Rui Caetano Oliveira

引用次数: 0

The Prognostic Role of Prognostic Nutritional Index and Controlling Nutritional Status in Predicting Survival in Older Adults with Oncological Disease: A Systematic Review 预后营养指数和控制营养状况在预测老年肿瘤患者生存期中的预后作用：系统综述

Onco Pub Date : 2024-06-02 DOI: 10.3390/onco4020009

Ana Filipa Ferreira, Tatiana Fernandes, Maria do Carmo Carvalho, Helena Soares Loureiro

{"title":"The Prognostic Role of Prognostic Nutritional Index and Controlling Nutritional Status in Predicting Survival in Older Adults with Oncological Disease: A Systematic Review","authors":"Ana Filipa Ferreira, Tatiana Fernandes, Maria do Carmo Carvalho, Helena Soares Loureiro","doi":"10.3390/onco4020009","DOIUrl":"https://doi.org/10.3390/onco4020009","url":null,"abstract":"The increase in new cancer diagnoses in the elderly calls for new, accessible, and easy-to-use prognostic tools that contribute to lowering the burden of the disease. Recognising the importance of inflammation and nutritional status in the progression of the disease, the purpose of this systematic review was to synthesise the evidence on the prognostic role of Prognostic Nutritional Index (PNI) and Controlling Nutritional Status (CONUT) in predicting survival of older adult cancer patients. A comprehensive search was conducted in PubMed and Web of Science Core Collection databases until 22 February 2024. The articles included in this review (n = 38) examined the relationships of PNI and CONUT with survival outcomes in elderly cancer patients. Despite high heterogeneity between the studies, most concluded that low PNI values are associated with poor overall survival (OS), particularly in gastric cancer patients. Most studies did not find an association between PNI and cancer-specific survival, progression-free survival, disease-free survival, recurrence-free survival, and mortality. Results regarding the prognostic role of CONUT in predicting survival were inconclusive. This study suggests that PNI could be used to predict OS in elderly cancer patients, while more studies are needed to assess the prognostic role of CONUT.","PeriodicalId":74339,"journal":{"name":"Onco","volume":"19 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141273381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

How Reliable Are Predictions of CD8+ T Cell Epitope Recognition? Lessons for Cancer 对 CD8+ T 细胞表位识别的预测有多可靠？对癌症的启示

Onco Pub Date : 2024-04-17 DOI: 10.3390/onco4020006

A. Lehmann, Paul V Lehmann, Stephen Todryk

引用次数: 0

Deficiency in DNA Damage Repair Proteins Promotes Prostate Cancer Cell Migration through Oxidative Stress DNA 损伤修复蛋白的缺乏通过氧化应激促进前列腺癌细胞迁移

Onco Pub Date : 2024-03-28 DOI: 10.3390/onco4020005

Philippa Lantwin, A. Kaczorowski, C. Nientiedt, C. Schwab, Martina Kirchner, V. Schütz, M. Görtz, Markus Hohenfellner, A. Duensing, A. Stenzinger, Stefan Duensing

{"title":"Deficiency in DNA Damage Repair Proteins Promotes Prostate Cancer Cell Migration through Oxidative Stress","authors":"Philippa Lantwin, A. Kaczorowski, C. Nientiedt, C. Schwab, Martina Kirchner, V. Schütz, M. Görtz, Markus Hohenfellner, A. Duensing, A. Stenzinger, Stefan Duensing","doi":"10.3390/onco4020005","DOIUrl":"https://doi.org/10.3390/onco4020005","url":null,"abstract":"Introduction: DNA damage repair gene deficiency defines a subgroup of prostate cancer patients with early metastatic progression and unfavorable disease outcome. Whether deficiency in DNA damage repair genes directly promotes metastatic dissemination is not completely understood. Methods: The migratory behavior of prostate cancer cells was analyzed after siRNA-mediated knockdown of DNA damage repair and checkpoint proteins, including BRCA2, ATM, and others, using transwell migration assays, scratch assays and staining for F-actin to ascertain cell circularity. Cells deficient in BRCA2 or ATM were tested for oxidative stress by measuring reactive oxygen species (ROS). The effects of ROS inhibition on cell migration were analyzed using the antioxidant N-acetylcysteine (NAC). The correlation between BRCA2 deficiency and oxidative stress was ascertained via immunohistochemistry for methylglyoxal (MG)-modified proteins in 15 genetically defined primary prostate cancers. Results: Prostate cancer cells showed a significantly increased migratory activity after the knockdown of BRCA2 or ATM. There was a significant increase in ROS production in LNCaP cells after BRCA2 knockdown and in PC-3 cells after BRCA2 or ATM knockdown. Remarkably, the ROS scavenger NAC abolished the enhanced motility of prostate cancer cells after the knockdown of BRCA2 or ATM. Primary prostate cancers harboring genetic alterations in BRCA2 showed a significant increase in MG-modified proteins, indicating enhanced oxidative stress in vivo. Conclusions: Our results indicate that DNA damage repair gene deficiency may contribute to the metastatic dissemination of prostate cancer through enhanced tumor cell migration involving oxidative stress.","PeriodicalId":74339,"journal":{"name":"Onco","volume":"21 19","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140372990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dendritic Cell Immunotherapy for Ovarian Cancer: An Overview of Our Achievements 树突状细胞免疫疗法治疗卵巢癌：我们的成就概览

Onco Pub Date : 2024-03-21 DOI: 10.3390/onco4010004

J. Bartůňková

{"title":"Dendritic Cell Immunotherapy for Ovarian Cancer: An Overview of Our Achievements","authors":"J. Bartůňková","doi":"10.3390/onco4010004","DOIUrl":"https://doi.org/10.3390/onco4010004","url":null,"abstract":"Epithelial ovarian carcinoma (EOC) is the fifth leading cause of cancer-related death in women, largely reflecting the early dissemination of this malignant disease to the peritoneum. Due to its immunological features, EOC has poor response to immune checkpoint inhibitors (ICIs), including a limited tumor mutational burden (TMB), poor infiltration by immune cells, and active immunosuppression. Thus, novel strategies are needed to overcome the frequent lack of pre-existing immunity in patients with EOC. We developed and tested an autologous dendritic cell (DC)-based vaccine (DCVAC), which has recently been shown to be safe and to significantly improve progression-free survival (PFS) in two independent randomized phase II clinical trials enrolling patients with EOC (SOV01, NCT02107937; SOV02, NCT02107950). In addition, our exploratory data analyses suggest that the clinical benefits of the DCVAC were more pronounced in patients with EOC with lower-than-median TMBs and reduced CD8+ T cell infiltration. Thus, the DC-based vaccine stands out as a promising clinical tool to jumpstart anticancer immunity in patients with immunologically “cold” EOC. Our findings underscore the need for personalized immunotherapy and the clinical relevance of potential tumor-related biomarkers within the immunotherapy field. Additional clinical trials are needed to address these strategies as well as the potential value of the TMB and immune infiltration at baseline as biomarkers for guiding the clinical management of EOC.","PeriodicalId":74339,"journal":{"name":"Onco","volume":"137 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140223704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

When Therapy-Induced Cancer Cell Apoptosis Fuels Tumor Relapse 治疗诱导的癌细胞凋亡何时助长肿瘤复发

Onco Pub Date : 2024-02-04 DOI: 10.3390/onco4010003

R. Mirzayans

引用次数: 0

When Therapy-Induced Cancer Cell Apoptosis Fuels Tumor Relapse 治疗诱导的癌细胞凋亡何时助长肿瘤复发

Onco Pub Date : 2024-02-04 DOI: 10.3390/onco4010003

R. Mirzayans

{"title":"When Therapy-Induced Cancer Cell Apoptosis Fuels Tumor Relapse","authors":"R. Mirzayans","doi":"10.3390/onco4010003","DOIUrl":"https://doi.org/10.3390/onco4010003","url":null,"abstract":"Most therapeutic strategies for solid tumor malignancies are designed based on the hypothesis that cancer cells evade apoptosis to exhibit therapy resistance. This is somewhat surprising given that clinical studies published since the 1990s have demonstrated that increased apoptosis in solid tumors is associated with cancer aggressiveness and poor clinical outcome. This is consistent with more recent reports demonstrating non-canonical (pro-survival) roles for apoptotic caspases, including caspase 3, as well as the ability of cancer cells to recover from late stages of apoptosis via a process called anastasis. These activities are essential for the normal development and maintenance of a healthy organism, but they also enable malignant cells (including cancer stem cells) to resist anticancer treatment and potentially contribute to clinical dormancy (minimal residual disease). Like apoptosis, therapy-induced cancer cell dormancy (durable proliferation arrest reflecting various manifestations of genome chaos) is also not obligatorily a permanent cell fate. However, as briefly discussed herein, compelling pre-clinical studies suggest that (reversible) dormancy might be the “lesser evil” compared to treacherous apoptosis.","PeriodicalId":74339,"journal":{"name":"Onco","volume":"87 2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139806897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Significance of PET/CT Imaging in Myeloma Assessment: Exploring Novel Applications beyond Osteolytic Lesion Detection and Treatment Response PET/CT 成像在骨髓瘤评估中的意义：探索溶骨病变检测和治疗反应之外的新应用

Onco Pub Date : 2024-01-09 DOI: 10.3390/onco4010002

M. Zirakchian Zadeh

{"title":"Significance of PET/CT Imaging in Myeloma Assessment: Exploring Novel Applications beyond Osteolytic Lesion Detection and Treatment Response","authors":"M. Zirakchian Zadeh","doi":"10.3390/onco4010002","DOIUrl":"https://doi.org/10.3390/onco4010002","url":null,"abstract":"In multiple myeloma (MM), specific cytokines produced by plasma cells disrupt the equilibrium between osteoblasts and osteoclasts. As a result, MM patients experience an increase in osteoclast activity and a decrease in osteoblast activity. This disparity is fundamental to the development of myeloma bone disease. Lytic lesions, which are a feature of MM, can result in pathologic fractures and excruciating pain. For many years, whole-body X-ray radiography has been the standard imaging method for identifying lytic lesions. However, its sensitivity is limited because it can only detect lesions once the bone mass has been reduced by 30% to 50%. Hence, utilizing advanced and sensitive imaging modalities, such as positron emission tomography (PET) fused with computed tomography (CT), is crucial for the early detection of osteolytic lesions. Among radiotracers used in PET imaging, 1⁸F-fluorodeoxyglucose ([18F]FDG) is the most commonly employed in the field of oncology. Currently, most guidelines include [18F]FDG PET/CT in the assessment of myeloma patients, particularly for detecting osteolytic lesions, evaluating treatment response, and assessing extramedullary and residual disease. Nonetheless, in recent years, new applications of PET/CT for evaluating myeloma have been investigated. These include assessing aspects such as bone turnover, dual-time-point imaging (early and delayed scans), the impact of chemotherapy on the brain (commonly known as ‘chemo brain’), innovative PET radiotracers, and the use of artificial intelligence technology. This article aims to provide a comprehensive review of both conventional and innovative uses of PET/CT in evaluating multiple myeloma.","PeriodicalId":74339,"journal":{"name":"Onco","volume":"67 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139445096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0