Frontiers in Oncology最新文献

{"title":"Dual TTK/PLK1 inhibition has potent anticancer activity in TNBC as monotherapy and in combination","authors":"E. Zanini, N. Forster-Gross, F. Bachmann, Adrian Brüngger, P. Mcsheehy, K. Litherland, K. Burger, Anna C. Groner, M. Roceri, Luc Bury, Martin Stieger, N. Willemsen-Seegers, J. de Man, D. Vu-Pham, Helma W. E. van Riel, G. Zaman, R. Buijsman, L. Kellenberger, Heidi A. Lane","doi":"10.3389/fonc.2024.1447807","DOIUrl":"https://doi.org/10.3389/fonc.2024.1447807","url":null,"abstract":"Threonine tyrosine kinase (TTK) and polo-like kinase 1 (PLK1) are common essential kinases that collaborate in activating the spindle assembly checkpoint (SAC) at the kinetochore, ensuring appropriate chromosome alignment and segregation prior to mitotic exit. Targeting of either TTK or PLK1 has been clinically evaluated in cancer patients; however, dual inhibitors have not yet been pursued. Here we present the in vitro and in vivo characterization of a first in class, dual TTK/PLK1 inhibitor (BAL0891).Mechanism of action studies utilized biochemical kinase and proteomics-based target-engagement assays. Cellular end-point assays included immunoblot- and flow cytometry-based cell cycle analyses and SAC integrity evaluation using immunoprecipitation and immunofluorescence approaches. Anticancer activity was assessed in vitro using cell growth assays and efficacy was evaluated, alone and in combination with paclitaxel and carboplatin, using mouse models of triple negative breast cancer (TNBC).BAL0891 elicits a prolonged effect on TTK, with a transient activity on PLK1. This unique profile potentiates SAC disruption, forcing tumor cells to aberrantly exit mitosis with faster kinetics than observed with a TTK-specific inhibitor. Broad anti-proliferative activity was demonstrated across solid tumor cell lines in vitro. Moreover, intermittent intravenous single-agent BAL0891 treatment of the MDA-MB-231 mouse model of TNBC induced profound tumor regressions associated with prolonged TTK and transient PLK1 in-tumor target occupancy. Furthermore, differential tumor responses across a panel of thirteen TNBC patient-derived xenograft models indicated profound anticancer activity in a subset (~40%). Using a flexible dosing approach, pathologically confirmed cures were observed in combination with paclitaxel, whereas synergy with carboplatin was schedule dependent.Dual TTK/PLK1 inhibition represents a novel approach for the treatment of human cancer, including TNBC patients, with a potential for potent anticancer activity and a favorable therapeutic index. Moreover, combination approaches may provide an avenue to expand responsive patient populations.","PeriodicalId":507440,"journal":{"name":"Frontiers in Oncology","volume":"35 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141923021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deep learning-assisted diagnosis of benign and malignant parotid gland tumors based on automatic segmentation of ultrasound images: a multicenter retrospective study","authors":"Wei Wei, Jingya Xu, Fei Xia, Jun Liu, Zekai Zhang, Jing Wu, Tianjun Wei, Huijun Feng, Qiang Ma, Feng Jiang, Xiangming Zhu, Xia Zhang","doi":"10.3389/fonc.2024.1417330","DOIUrl":"https://doi.org/10.3389/fonc.2024.1417330","url":null,"abstract":"To construct deep learning-assisted diagnosis models based on automatic segmentation of ultrasound images to facilitate radiologists in differentiating benign and malignant parotid tumors.A total of 582 patients histopathologically diagnosed with PGTs were retrospectively recruited from 4 centers, and their data were collected for analysis. The radiomics features of six deep learning models (ResNet18, Inception_v3 etc) were analyzed based on the ultrasound images that were obtained under the best automatic segmentation model (Deeplabv3, UNet++, and UNet). The performance of three physicians was compared when the optimal model was used and not. The Net Reclassification Index (NRI) and Integrated Discrimination Improvement (IDI) were utilized to evaluate the clinical benefit of the optimal model.The Deeplabv3 model performed optimally in terms of automatic segmentation. The ResNet18 deep learning model had the best prediction performance, with an area under the receiver-operating characteristic curve of 0.808 (0.694−0.923), 0.809 (0.712−0.906), and 0.812 (0.680−0.944) in the internal test set and external test sets 1 and 2, respectively. Meanwhile, the optimal model-assisted clinical and overall benefits were markedly enhanced for two out of three radiologists (in internal validation set, NRI: 0.259 and 0.213 [p = 0.002 and 0.017], IDI: 0.284 and 0.201 [p = 0.005 and 0.043], respectively; in external test set 1, NRI: 0.183 and 0.161 [p = 0.019 and 0.008], IDI: 0.205 and 0.184 [p = 0.031 and 0.045], respectively; in external test set 2, NRI: 0.297 and 0.297 [p = 0.038 and 0.047], IDI: 0.332 and 0.294 [p = 0.031 and 0.041], respectively).The deep learning model constructed for automatic segmentation of ultrasound images can improve the diagnostic performance of radiologists for PGTs.","PeriodicalId":507440,"journal":{"name":"Frontiers in Oncology","volume":"4 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141923184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revisiting the potential of regulated cell death in glioma treatment: a focus on autophagy-dependent cell death, anoikis, ferroptosis, cuproptosis, pyroptosis, immunogenic cell death, and the crosstalk between them","authors":"Maowen Luo, X. Luan, Chaoge Yang, Xiaofan Chen, Suxin Yuan, Youlin Cao, Jing Zhang, Jiaying Xie, Qinglian Luo, Ligang Chen, Shenjie Li, Wei Xiang, Jie Zhou","doi":"10.3389/fonc.2024.1397863","DOIUrl":"https://doi.org/10.3389/fonc.2024.1397863","url":null,"abstract":"Gliomas are primary tumors that originate in the central nervous system. The conventional treatment options for gliomas typically encompass surgical resection and temozolomide (TMZ) chemotherapy. However, despite aggressive interventions, the median survival for glioma patients is merely about 14.6 months. Consequently, there is an urgent necessity to explore innovative therapeutic strategies for treating glioma. The foundational study of regulated cell death (RCD) can be traced back to Karl Vogt’s seminal observations of cellular demise in toads, which were documented in 1842. In the past decade, the Nomenclature Committee on Cell Death (NCCD) has systematically classified and delineated various forms and mechanisms of cell death, synthesizing morphological, biochemical, and functional characteristics. Cell death primarily manifests in two forms: accidental cell death (ACD), which is caused by external factors such as physical, chemical, or mechanical disruptions; and RCD, a gene-directed intrinsic process that coordinates an orderly cellular demise in response to both physiological and pathological cues. Advancements in our understanding of RCD have shed light on the manipulation of cell death modulation - either through induction or suppression - as a potentially groundbreaking approach in oncology, holding significant promise. However, obstacles persist at the interface of research and clinical application, with significant impediments encountered in translating to therapeutic modalities. It is increasingly apparent that an integrative examination of the molecular underpinnings of cell death is imperative for advancing the field, particularly within the framework of inter-pathway functional synergy. In this review, we provide an overview of various forms of RCD, including autophagy-dependent cell death, anoikis, ferroptosis, cuproptosis, pyroptosis and immunogenic cell death. We summarize the latest advancements in understanding the molecular mechanisms that regulate RCD in glioma and explore the interconnections between different cell death processes. By comprehending these connections and developing targeted strategies, we have the potential to enhance glioma therapy through manipulation of RCD.","PeriodicalId":507440,"journal":{"name":"Frontiers in Oncology","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141924714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical experience with adaptive MRI-guided pancreatic SBRT and the use of abdominal compression to reduce treatment volume","authors":"William S. Ferris, Benjamin George, Kristin A. Plichta, Joseph M. Caster, D. Hyer, Blake R. Smith, J. St-Aubin","doi":"10.3389/fonc.2024.1441227","DOIUrl":"https://doi.org/10.3389/fonc.2024.1441227","url":null,"abstract":"This work presents a method to treat stereotactic body radiation therapy (SBRT) for pancreatic cancer on a magnetic resonance-guided linear accelerator (MR-linac) using daily adaptation, real-time motion monitoring, and abdominal compression.The motion management and treatment planning process involves a magnetic resonance imaging (MRI) simulation with cine and 3D images, a computed tomography (CT) simulation with a breath-hold CT and a 4DCT, pre-treatment verification and planning MRI, and intrafraction MRI cine images.The results from 26 patients were included in this work. Our motion management process results in consistent motion analysis on the CT simulation, MRI simulation, and each treatment fraction. The liver dome was found to be an overestimate of tumor superior/inferior (SI) motion for most patients. Adding compression reduced SI liver dome motion by 6.2 mm on average. Clinical outcomes are similar to those observed in the literature.In this work, we demonstrate how pancreatic SBRT can be successfully treated on an MR-linac using abdominal compression. This allows for an increased duty cycle compared to gating and/or breath-hold techniques.","PeriodicalId":507440,"journal":{"name":"Frontiers in Oncology","volume":"3 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141921197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Implementing fencing as adapted physical activity in non-metastatic breast cancer patients: design and early rehabilitation strategy of the FENICE study protocol","authors":"M. Berretta, Daniele Garozzo, Calogero Foti, Mario Roselli, M. Materazzo, Giulia Vita, Ferdinando Iellamo, Marco Scordari, Giordana Di Mauro, Giovanna Spatari, Alessandro Ottaiano, A. Noce, Marco Pelicciaro, Alessia Bignucolo, Gianluca Vanni, O. Buonomo","doi":"10.3389/fonc.2024.1407919","DOIUrl":"https://doi.org/10.3389/fonc.2024.1407919","url":null,"abstract":"Improving prognosis of BC patients has drawn the attention of health care professionals on disease related long-term side effects and on the multiple treatments BC patients must undergo. Despite advances in procedures, surgery still has multiple detrimental effects, including pain, edema, and limited mobility. For this reason, fostering adapted physical activity (APA) and healthy lifestyle (including a balanced diet and weight management) should become an everyday purpose of healthcare professionals. Fencing may be a well-suited activity to counteract fatigue, pain, and limited arm mobility.The FENICE study is a mono-center, randomized clinical trial targeting women with BC stages I-III within four weeks from BC surgery. Participants in the control arm will receive the usual recommendations based on the good clinical practice guidelines. In the study arm, participants will be treated with the usual clinical and therapeutic recommendations together with APA and correct lifestyle suggestions.The primary objective of the study is to compare whether implementation of APA and healthy lifestyle in BC patient after surgery will result in an overall improvement of physical and mental status.Fencing and its early application in postoperative period may represent a feasible strategy to be implemented in the rehabilitation journey of BC patients.The study protocol FENICE has been approved by an Italian Ethics Committee on May 2023 (R.S 100.23 5th May 2023).","PeriodicalId":507440,"journal":{"name":"Frontiers in Oncology","volume":"3 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141925628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chimeric antigen receptor T-cells: a review on current status and future directions for relapsed/refractory multiple myeloma","authors":"Issam S. Hamadeh, Reed Friend, S. Mailankody, S. Atrash","doi":"10.3389/fonc.2024.1455464","DOIUrl":"https://doi.org/10.3389/fonc.2024.1455464","url":null,"abstract":"Although multiple myeloma is an incurable disease, the past decade has witnessed significant improvement in patient outcomes. This was brought about by the development of T-cell redirection therapies such as chimeric antigen receptor (CAR) T-cells, which can leverage the natural ability of the immune system to fight myeloma cells. The approval of the B-cell maturation antigen (BCMA)-directed CAR T, idecabtagene vicleucel (ide-cel), and ciltacabtagene autoleucel (cilta-cel) has resulted in a paradigm shift in the treatment of relapsed/refractory multiple myeloma. Overall response rates ranging from 73 to 97% are currently achievable. However, the limitations of KarMMa-1 and CARTITUDE-1 studies spurred the generation of real-world data to provide some insights into the effectiveness of ide-cel and cilta-cel among patients who were excluded from clinical trials, particularly those who received prior BCMA-targeted or other T-cell redirection therapies. Despite their unprecedented clinical efficacy in heavily pretreated patients, responses to CAR T remain non-durable. Although the underlying mechanisms of resistance to these agents haven’t been fully elucidated, studies have suggested that resistance patterns could be multifaceted, implicating T-cell exhaustion and tumor intrinsic mechanisms such as BCMA target loss, upregulation of gamma-secretase, and others. Herein, we provide a succinct overview of the development of CAR T-cells, manufacturing process, and associated toxicities/complications. In this review, we also recapitulate the existing literature pertaining MM CAR-T as well as emerging data from some of the ongoing clinical trials designed to mitigate the shortcomings of these agents, and improve the clinical efficacy of CAR T, especially in the relapsed/refractory setting.","PeriodicalId":507440,"journal":{"name":"Frontiers in Oncology","volume":"35 23","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141928667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Recent advances in surgical management of NSCLC","authors":"Marcello Migliore, Domenico Galetta, Masayuki Chida","doi":"10.3389/fonc.2024.1454905","DOIUrl":"https://doi.org/10.3389/fonc.2024.1454905","url":null,"abstract":"","PeriodicalId":507440,"journal":{"name":"Frontiers in Oncology","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141927142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Imaging features and clinical evaluation of pulmonary nodules in children","authors":"Muheremu Dilimulati, Shuhua Yuan, Hejun Jiang, Yahua Wang, Hui Ma, Shiyu Shen, Jilei Lin, Jiande Chen, Yong Yin","doi":"10.3389/fonc.2024.1385600","DOIUrl":"https://doi.org/10.3389/fonc.2024.1385600","url":null,"abstract":"With the widespread use of computed tomography (CT), the detection rate of pulmonary nodules in children has gradually increased. Due to the lack of epidemiological evidence and clinical guideline on pulmonary nodule treatment in children, we aimed to provide a reference for the clinical diagnosis and management of pediatirc pulmonary nodules.This retrospective study collected consecutive cases from April 2012 to July 2021 in the Shanghai Children’s Medical Center. The sample included children with pulmonary nodules on chest CT scans and met the inclusion criteria. All patients were categorized into tumor and non-tumor groups by pre-CT clinical diagnosis. Nodule characteristics between groups were analyzed. To establish a clinical assessment model for the benign versus malignant pulmonary nodules, patients who have been followed-up for three months were detected and a decision tree model for nodule malignancy prediction was constructed and validated.The sample comprised 1341 patients with an average age of 7.2 ± 4.6 years. More than half of them (51.7%) were diagnosed with malignancies before CT scan. 48.3% were diagnosed with non-tumor diseases or healthy. Compared to non-tumor group, children with tumor were more likely to have multiple nodules in both lungs, with larger size and often be accompanied by osteolytic or mass lesions. Based on the decision tree model, patients’ history of malignancies, nodules diameter size≥5mm, and specific nodule distribution (multiple in both lungs, multiple in the right lung or solitary in the upper or middle right lobe) were important potential predictors for malignity. In the validation set, sensitivity, specificity and AUC were 0.855, 0.833 and 0.828 (95%CI: 0.712-0.909), respectively.This study conducted a clinical assessment model to differentiate benignity and malignancy of pediatric pulmonary nodules. We suggested that a nodule’s diameter, distribution and patient’s history of malignancies are predictable factors in benign or malignant determination.","PeriodicalId":507440,"journal":{"name":"Frontiers in Oncology","volume":"54 39","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141929036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Solitary fibrous tumor of the pineal gland: a case report and review of the literature","authors":"Yixiao He, Pengchen He, Anqun Wang, Yuzhu Ji, Gang Xie, Lili Zou","doi":"10.3389/fonc.2024.1392540","DOIUrl":"https://doi.org/10.3389/fonc.2024.1392540","url":null,"abstract":"Solitary fibrous tumor (SFT) is a type of fibroblastic neoplasm that can occur in various parts of the body, with SFT of the pineal gland being exceedingly rare. We report the case of a 58-year-old male presenting with recurrent hiccups, acid reflux, and headache. Magnetic resonance imaging revealed an occupying lesion in the pineal region, suggestive of a neoplastic process. Intraoperatively, the lesion was located in the pineal region, exhibiting a grayish-red color, and was largely resected. Pathological examination confirmed the diagnosis of solitary fibrous tumor (CNS WHO Grade 1). Postoperatively, the patient was supplemented with radiotherapy, and long-term follow-up showed no signs of recurrence or metastasis.","PeriodicalId":507440,"journal":{"name":"Frontiers in Oncology","volume":"17 18","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141927401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Crosstalk between breast cancer-derived microRNAs and brain microenvironmental cells in breast cancer brain metastasis","authors":"Munazza Khan, Grace L Wong, Chuling Zhuang, Mariana K. Najjar, Hui-Wen Lo","doi":"10.3389/fonc.2024.1436942","DOIUrl":"https://doi.org/10.3389/fonc.2024.1436942","url":null,"abstract":"Breast cancer is the most frequent malignancy in women, constituting 15.2% of all new cancers diagnosed in the United States. Distant breast cancer metastasis accounts for the majority of breast cancer-related deaths; brain metastasis is the third most common site for metastatic breast cancer but is associated with worst prognosis of approximately eight months of survival. Current treatment options for breast cancer brain metastasis (BCBM) are limited and ineffective. To help identify new and effective therapies for BCBM, it is important to investigate the mechanisms by which breast cancer cells metastasize to the brain and thrive in the brain microenvironment. To this end, studies have reported that primary breast tumor cells can prime brain microenvironmental cells, including, astrocytes and microglia, to promote the formation of BCBM through the release of extracellular vesicle-microRNAs (miRNAs). Breast tumor-derived miRNAs can also promote breast cancer cell invasion through the blood-brain barrier by disrupting the integrity of the brain microvascular endothelial cells. In this review, we summarize current literature on breast cancer-derived BCBM-promoting miRNAs, cover their roles in the complex steps of BCBM particularly their interactions with microenvironmental cells within the brain metastatic niche, and finally discuss their therapeutic applications in the management of BCBM.","PeriodicalId":507440,"journal":{"name":"Frontiers in Oncology","volume":"45 24","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141928279","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}