Bruno Takao Real Karia, Camila Albuquerque Pinto, C. Gigek, Fernanda Wisnieski, M. Arruda Cardoso Smith
Gastric cancer is one of the most common cancers and the third cause of cancer-related death worldwide. The treatment of GC patients improved due to advancements in surgery, radiotherapy and chemotherapy. However, the long-term survival rate of patients with gastric cancer remains around 20%. Thus, development of novel therapeutic approaches is of great interest, in order to reduce the need for mutilating surgeries and morbid adjuvant therapies. For many years, it was believed that the RNA was a mere intermediate molecule in the genetic information flow. However, during the past decades, with the advent of new sequencing technologies, it was revealed that non-coding RNAs play important roles in many different biological processes. The Wnt/β-catenin signaling pathway has been reported to regulate crucial events during neoplasic development, such as cell differentiation, proliferation, invasion, migration, apoptosis, and angiogenesis. In this review, we will focus on microRNAs and long non-coding RNAs that have been implicated in gastric cancer tumorigenesis via modulation of the Wnt/β-catenin signaling pathway, which provided some biomarkers to prognosis, diagnosis, and therapy.
{"title":"Non-Coding RNAs and Wnt/β-Catenin Signaling Pathway in Gastric Cancer: From EMT to Drug Resistance","authors":"Bruno Takao Real Karia, Camila Albuquerque Pinto, C. Gigek, Fernanda Wisnieski, M. Arruda Cardoso Smith","doi":"10.3390/onco1020012","DOIUrl":"https://doi.org/10.3390/onco1020012","url":null,"abstract":"Gastric cancer is one of the most common cancers and the third cause of cancer-related death worldwide. The treatment of GC patients improved due to advancements in surgery, radiotherapy and chemotherapy. However, the long-term survival rate of patients with gastric cancer remains around 20%. Thus, development of novel therapeutic approaches is of great interest, in order to reduce the need for mutilating surgeries and morbid adjuvant therapies. For many years, it was believed that the RNA was a mere intermediate molecule in the genetic information flow. However, during the past decades, with the advent of new sequencing technologies, it was revealed that non-coding RNAs play important roles in many different biological processes. The Wnt/β-catenin signaling pathway has been reported to regulate crucial events during neoplasic development, such as cell differentiation, proliferation, invasion, migration, apoptosis, and angiogenesis. In this review, we will focus on microRNAs and long non-coding RNAs that have been implicated in gastric cancer tumorigenesis via modulation of the Wnt/β-catenin signaling pathway, which provided some biomarkers to prognosis, diagnosis, and therapy.","PeriodicalId":74339,"journal":{"name":"Onco","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44081593","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}
L. Filippi, V. Frantellizzi, Marko Magdi Abdou Sidrak, Joana Gorica, Stefano Scippa, A. Chiaravalloti, O. Schillaci, O. Bagni, G. de Vincentis
Neuroblastoma (NB) represents the most common extracranial tumor of childhood. Prognosis is quite variable, ranging from spontaneous regression to aggressive behavior with wide metastatization, high mortality, and limited therapeutic options. Radiotheranostics combines a radiopharmaceutical pair in a unique approach, suitable both for diagnosis and therapy. For many years, metaiodobenzylguanidine (MIBG), labeled with 123I for imaging or 131I for therapy, has represented the main theranostic agent in NB, since up to 90% of NB incorporates the aforementioned radiopharmaceutical. In recent years, novel theranostic agents hold promise in moving the field of NB radiotheranostics forward. In particular, SarTATE, consisting of octreotate targeting somatostatin receptors, has been applied with encouraging results, with 64Cu-SARTATE being used for disease detection and with 67Cu-SARTATE being used for therapy. Furthermore, recent evidence has highlighted the potential of targeted alpha therapy (TAT) for treating cancer by virtue of alpha particles’ high ionizing density and high probability of killing cells along their track. On this path, 211At-astatobenzylguanidine (MABG) has been developed as a potential agent for TAT and is actually under evaluation in preclinical NB models. In this review, we performed a web-based and desktop literature research concerning radiotheranostic approaches in NB, covering both the radiopharmaceuticals already implemented in clinical practice (i.e.,123/1311-MIBG) and those still in a preliminary or preclinical phase.
{"title":"Radiotheranostic Agents Targeting Neuroblastoma: State-of-the-Art and Emerging Perspectives","authors":"L. Filippi, V. Frantellizzi, Marko Magdi Abdou Sidrak, Joana Gorica, Stefano Scippa, A. Chiaravalloti, O. Schillaci, O. Bagni, G. de Vincentis","doi":"10.3390/onco1020011","DOIUrl":"https://doi.org/10.3390/onco1020011","url":null,"abstract":"Neuroblastoma (NB) represents the most common extracranial tumor of childhood. Prognosis is quite variable, ranging from spontaneous regression to aggressive behavior with wide metastatization, high mortality, and limited therapeutic options. Radiotheranostics combines a radiopharmaceutical pair in a unique approach, suitable both for diagnosis and therapy. For many years, metaiodobenzylguanidine (MIBG), labeled with 123I for imaging or 131I for therapy, has represented the main theranostic agent in NB, since up to 90% of NB incorporates the aforementioned radiopharmaceutical. In recent years, novel theranostic agents hold promise in moving the field of NB radiotheranostics forward. In particular, SarTATE, consisting of octreotate targeting somatostatin receptors, has been applied with encouraging results, with 64Cu-SARTATE being used for disease detection and with 67Cu-SARTATE being used for therapy. Furthermore, recent evidence has highlighted the potential of targeted alpha therapy (TAT) for treating cancer by virtue of alpha particles’ high ionizing density and high probability of killing cells along their track. On this path, 211At-astatobenzylguanidine (MABG) has been developed as a potential agent for TAT and is actually under evaluation in preclinical NB models. In this review, we performed a web-based and desktop literature research concerning radiotheranostic approaches in NB, covering both the radiopharmaceuticals already implemented in clinical practice (i.e.,123/1311-MIBG) and those still in a preliminary or preclinical phase.","PeriodicalId":74339,"journal":{"name":"Onco","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47111103","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}
Anne Stensvold, N. Aggerholm-Pedersen, Anne Winther-Larsen, Birgitte Sandfeld-Paulsen
Improved prognostication of small cell lung cancer (SCLC) patients could strengthen the treatment strategy and, thereby, potentially improve the overall survival (OS) of these patients. C-reactive protein (CRP) has been proposed as a prognostic indicator of inferior survival, although so far, only based on data from smaller studies. Data on SCLC patients diagnosed from January 2009 to June 2018 were extracted from the Danish Lung Cancer Registry and the clinical laboratory information system. CRP measurements were divided at the clinical cut-off value of 8 mg/L or 75 nmol/L) and stratified into quartiles. Cox proportional hazards model assessed the prognostic value of the CRP level. C-statistics further evaluated the biomarker’s prognostic value. In total, 923 patients were included. A pre-treatment CRP level above the clinical cut-off significantly correlated to inferior OS (adjusted hazard ratio (HR) = 1.25 (95% confidence interval (CI): 1.08–1.46). When divided into quartiles, a level-dependent correlation was observed with only the highest quartiles significantly associated with OS (3rd quartile: adjusted HR = 1.26 (95% CI: 1.03–1.55) 4th quartile: adjusted HR = 1.44 (95% CI: 1.17–1.77)). Adding CRP level to already well-established prognostic factors improved the prognostication of SCLC patients. In conclusion, high pre-treatment CRP level is an independent prognostic factor in SCLC patients.
{"title":"Pre-Treatment C-Reactive Protein Predicts Survival in Small Cell Lung Cancer Patients","authors":"Anne Stensvold, N. Aggerholm-Pedersen, Anne Winther-Larsen, Birgitte Sandfeld-Paulsen","doi":"10.3390/onco1020010","DOIUrl":"https://doi.org/10.3390/onco1020010","url":null,"abstract":"Improved prognostication of small cell lung cancer (SCLC) patients could strengthen the treatment strategy and, thereby, potentially improve the overall survival (OS) of these patients. C-reactive protein (CRP) has been proposed as a prognostic indicator of inferior survival, although so far, only based on data from smaller studies. Data on SCLC patients diagnosed from January 2009 to June 2018 were extracted from the Danish Lung Cancer Registry and the clinical laboratory information system. CRP measurements were divided at the clinical cut-off value of 8 mg/L or 75 nmol/L) and stratified into quartiles. Cox proportional hazards model assessed the prognostic value of the CRP level. C-statistics further evaluated the biomarker’s prognostic value. In total, 923 patients were included. A pre-treatment CRP level above the clinical cut-off significantly correlated to inferior OS (adjusted hazard ratio (HR) = 1.25 (95% confidence interval (CI): 1.08–1.46). When divided into quartiles, a level-dependent correlation was observed with only the highest quartiles significantly associated with OS (3rd quartile: adjusted HR = 1.26 (95% CI: 1.03–1.55) 4th quartile: adjusted HR = 1.44 (95% CI: 1.17–1.77)). Adding CRP level to already well-established prognostic factors improved the prognostication of SCLC patients. In conclusion, high pre-treatment CRP level is an independent prognostic factor in SCLC patients.","PeriodicalId":74339,"journal":{"name":"Onco","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47962467","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}
Shengzhi Liu, Xun Sun, Ke-xin Li, Chien-Chi Lin, S. Na, Bai-Yan Li, H. Yokota
Tumor cells regulate their progression not only by the factors within their cell bodies but also by the secretome they produce and secrete. While their secretome significantly alters the fate of tumor cells themselves, they also regulate the growth of surrounding cells including both companion cancer and non-cancer cells. Tumor cell secretome consists of varying molecules that have been reported mostly tumor-promotive. Furthermore, their pro-tumor capability is enhanced by the application of chemotherapeutic agents. However, multiple lines of emerging evidence suggest that the tumor cell secretome can be tumor-suppressive in response to paracrine and endocrine signaling. This review introduces both tumor-promotive and tumor-suppressive secretomes, focusing on multi-tasking proteins in the intracellular and extracellular domains. We describe tumorigenic signaling that governs the nature of the tumor cell secretome and discuss the possibility of inducing tumor-suppressive proteomes as a novel option for cancer treatment. We evaluated the counterintuitive procedure to generate tumor-suppressive proteomes from a unique type of tumor-modifying cells, which are named “induced tumor-suppressing cells” (iTSCs).
{"title":"Tumor Cell Secretomes in Response to Anti- and Pro-Tumorigenic Agents","authors":"Shengzhi Liu, Xun Sun, Ke-xin Li, Chien-Chi Lin, S. Na, Bai-Yan Li, H. Yokota","doi":"10.3390/onco1020009","DOIUrl":"https://doi.org/10.3390/onco1020009","url":null,"abstract":"Tumor cells regulate their progression not only by the factors within their cell bodies but also by the secretome they produce and secrete. While their secretome significantly alters the fate of tumor cells themselves, they also regulate the growth of surrounding cells including both companion cancer and non-cancer cells. Tumor cell secretome consists of varying molecules that have been reported mostly tumor-promotive. Furthermore, their pro-tumor capability is enhanced by the application of chemotherapeutic agents. However, multiple lines of emerging evidence suggest that the tumor cell secretome can be tumor-suppressive in response to paracrine and endocrine signaling. This review introduces both tumor-promotive and tumor-suppressive secretomes, focusing on multi-tasking proteins in the intracellular and extracellular domains. We describe tumorigenic signaling that governs the nature of the tumor cell secretome and discuss the possibility of inducing tumor-suppressive proteomes as a novel option for cancer treatment. We evaluated the counterintuitive procedure to generate tumor-suppressive proteomes from a unique type of tumor-modifying cells, which are named “induced tumor-suppressing cells” (iTSCs).","PeriodicalId":74339,"journal":{"name":"Onco","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41350809","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}
Since the very beginnings of cancer therapy with chemotherapy, tumors have been treated according to the organ or tissue of origin. The advent of precision medicine however, has recently led to growing promise for tumor-agnostic biomarkers for targeted therapies and immunotherapies, such as NTRK fusions. Despite this, prominent examples such as BRAF V600E mutations in melanoma compared to colorectal cancer, in which the site of tumor origin dramatically influences the efficacy of targeted therapies, heeds caution against disregarding the importance of cell of origin. Indeed, another illustrative example, is the almost complete absence outside of cancers originating from the lung of the classical activating EGFR mutations—exon 19 deletions and exon 21 L858R mutations. Consequently, an understanding of lineage dependency and lineage-survival oncogenes may still offer significant mechanistic insights into the malignant transformation of tumors to ultimately identify further therapeutic vulnerabilities.
{"title":"Tumor-Agnostic Biomarkers: Heed Caution, and Why Cell of Origin Still Matters","authors":"A. Tan","doi":"10.3390/onco1020008","DOIUrl":"https://doi.org/10.3390/onco1020008","url":null,"abstract":"Since the very beginnings of cancer therapy with chemotherapy, tumors have been treated according to the organ or tissue of origin. The advent of precision medicine however, has recently led to growing promise for tumor-agnostic biomarkers for targeted therapies and immunotherapies, such as NTRK fusions. Despite this, prominent examples such as BRAF V600E mutations in melanoma compared to colorectal cancer, in which the site of tumor origin dramatically influences the efficacy of targeted therapies, heeds caution against disregarding the importance of cell of origin. Indeed, another illustrative example, is the almost complete absence outside of cancers originating from the lung of the classical activating EGFR mutations—exon 19 deletions and exon 21 L858R mutations. Consequently, an understanding of lineage dependency and lineage-survival oncogenes may still offer significant mechanistic insights into the malignant transformation of tumors to ultimately identify further therapeutic vulnerabilities.","PeriodicalId":74339,"journal":{"name":"Onco","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46355461","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}
Malignant pleural mesothelioma (MPM) is a rare, aggressive cancer of the lung lining that is predominantly associated with occupational exposure to asbestos. MPM is responsible for thousands of deaths worldwide every year, with the median survival of MPM of 8–14 months. There are limited biomarkers available in the clinic to effectively diagnose MPM, an invasive biopsy procedure is usually required to provide a definitive diagnosis. Due to the long latency period associated with MPM disease presentation, the cancer is usually at an advanced stage at the time of diagnosis where treatment options are largely ineffective at controlling disease progression. Previous MPM-based pre-clinical studies have made significant strides in determining the exact molecular mechanisms associated with asbestos carcinogenesis. Exploring less invasive blood-based biomarkers and treatment strategies involving targeted therapy, immunotherapy, and virotherapy is particularly important. Research in these areas is of crucial importance in relation to improving the rate of novel diagnostic biomarkers and treatment strategies progressing through to clinical trials and ultimately into the clinical setting. This review comprehensively summarises both previous and current pre-clinical research developments that have specifically contributed to an improved understanding of MPM disease biology, and the development of novel diagnostic biomarkers and treatment strategies.
{"title":"Pre-Clinical Research Advancements Relating to Improving the Diagnosis and Treatment of Malignant Pleural Mesothelioma: A Review","authors":"Ben Johnson, Kenneth Lee, Y. Cheng","doi":"10.3390/onco1020006","DOIUrl":"https://doi.org/10.3390/onco1020006","url":null,"abstract":"Malignant pleural mesothelioma (MPM) is a rare, aggressive cancer of the lung lining that is predominantly associated with occupational exposure to asbestos. MPM is responsible for thousands of deaths worldwide every year, with the median survival of MPM of 8–14 months. There are limited biomarkers available in the clinic to effectively diagnose MPM, an invasive biopsy procedure is usually required to provide a definitive diagnosis. Due to the long latency period associated with MPM disease presentation, the cancer is usually at an advanced stage at the time of diagnosis where treatment options are largely ineffective at controlling disease progression. Previous MPM-based pre-clinical studies have made significant strides in determining the exact molecular mechanisms associated with asbestos carcinogenesis. Exploring less invasive blood-based biomarkers and treatment strategies involving targeted therapy, immunotherapy, and virotherapy is particularly important. Research in these areas is of crucial importance in relation to improving the rate of novel diagnostic biomarkers and treatment strategies progressing through to clinical trials and ultimately into the clinical setting. This review comprehensively summarises both previous and current pre-clinical research developments that have specifically contributed to an improved understanding of MPM disease biology, and the development of novel diagnostic biomarkers and treatment strategies.","PeriodicalId":74339,"journal":{"name":"Onco","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41991743","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}
Pub Date : 2021-07-26DOI: 10.20944/preprints202107.0578.v1
G. Lee, M. Mubasher, T. McKenzie, N. Schmitt, M. Sebelik, C. Flanagan, B. Osta, Maya B. Cothran, H. Green
Objective: The combination of docetaxel (DTX) with Laser-Activated NanoTherapy (LANT), as a treatment for head and neck cancer (HNC) may enhance the therapeutic efficacy of lower doses of DTX, thereby minimizing the effective dosage, side effects and treatment times. Material and methods: Three HNSCC cell lines, Detroit 562, FaDu, and CAL 27, were treated with four combinations of DTX + LANT to evaluate DTX dose reduction and cell viability. Results: The 1 nM DTX + 5 nM LANT combination was the most effective treatment, increasing cell death over its corresponding DTX monotreatment with approximately 86.6%, 80.7%, and 92.1% cell death for Detroit 562, FaDu, and CAL 27, respectively. In Detroit 562, the 1 nM DTX + 5 nM LANT combination treatment resulted in the highest percentage of DTX dose reduction at 84.6%; in FaDu and CAL 27, the 0.5 nM DTX + 5 nM LANT combination treatment resulted in the highest percentage of DTX dose reduction at 78.2% and 82.4%, respectively. Conclusion: LANT may increase the therapeutic efficacy of DTX at significantly lower doses, which could improve patient outcomes.
{"title":"Assessment of a Nano-Docetaxel Combined Treatment for Head and Neck Cancer","authors":"G. Lee, M. Mubasher, T. McKenzie, N. Schmitt, M. Sebelik, C. Flanagan, B. Osta, Maya B. Cothran, H. Green","doi":"10.20944/preprints202107.0578.v1","DOIUrl":"https://doi.org/10.20944/preprints202107.0578.v1","url":null,"abstract":"Objective: The combination of docetaxel (DTX) with Laser-Activated NanoTherapy (LANT), as a treatment for head and neck cancer (HNC) may enhance the therapeutic efficacy of lower doses of DTX, thereby minimizing the effective dosage, side effects and treatment times. Material and methods: Three HNSCC cell lines, Detroit 562, FaDu, and CAL 27, were treated with four combinations of DTX + LANT to evaluate DTX dose reduction and cell viability. Results: The 1 nM DTX + 5 nM LANT combination was the most effective treatment, increasing cell death over its corresponding DTX monotreatment with approximately 86.6%, 80.7%, and 92.1% cell death for Detroit 562, FaDu, and CAL 27, respectively. In Detroit 562, the 1 nM DTX + 5 nM LANT combination treatment resulted in the highest percentage of DTX dose reduction at 84.6%; in FaDu and CAL 27, the 0.5 nM DTX + 5 nM LANT combination treatment resulted in the highest percentage of DTX dose reduction at 78.2% and 82.4%, respectively. Conclusion: LANT may increase the therapeutic efficacy of DTX at significantly lower doses, which could improve patient outcomes.","PeriodicalId":74339,"journal":{"name":"Onco","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49366620","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}
Daniel Zeitouni, Michael P. Catalino, J. Wise, S. McCabe, Kathryn M. Pietrosimone, N. Rashid, S. Khagi
BACKGROUND: Glioblastoma (GBM) is driven by various genomic alterations. Next-generation sequencing (NGS) could yield targetable alterations that might impact outcomes. The goal of this study was to describe how NGS can inform targeted therapy (TT) in this patient population. METHODS: The medical records of patients with a diagnosis of GBM from 2017 to 2019 were reviewed. Records of patients with recurrent GBM and genomic alterations were evaluated. Objective response rates and disease control rates were determined. RESULTS: A total of 87 patients with GBM underwent NGS. Forty percent (n = 35) were considered to have actionable alterations. Of these 35, 40% (n = 14) had their treatment changed due to the alteration. The objective response rate (ORR) of this population was 43%. The disease control rate (DCR) was 100%. The absolute mean decrease in contrast-enhancing disease was 50.7% (95% CI 34.8–66.6). CONCLUSION: NGS for GBM, particularly in the recurrent setting, yields a high rate of actionable alterations. We observed a high ORR and DCR, reflecting the value of NGS when deciding on therapies to match genomic alterations. In conclusion, patient selection and the availability of NGS might impact outcomes in select patients with recurrent GBM.
{"title":"Clinical Application of Next-Generation Sequencing in Recurrent Glioblastoma","authors":"Daniel Zeitouni, Michael P. Catalino, J. Wise, S. McCabe, Kathryn M. Pietrosimone, N. Rashid, S. Khagi","doi":"10.3390/onco1010005","DOIUrl":"https://doi.org/10.3390/onco1010005","url":null,"abstract":"BACKGROUND: Glioblastoma (GBM) is driven by various genomic alterations. Next-generation sequencing (NGS) could yield targetable alterations that might impact outcomes. The goal of this study was to describe how NGS can inform targeted therapy (TT) in this patient population. METHODS: The medical records of patients with a diagnosis of GBM from 2017 to 2019 were reviewed. Records of patients with recurrent GBM and genomic alterations were evaluated. Objective response rates and disease control rates were determined. RESULTS: A total of 87 patients with GBM underwent NGS. Forty percent (n = 35) were considered to have actionable alterations. Of these 35, 40% (n = 14) had their treatment changed due to the alteration. The objective response rate (ORR) of this population was 43%. The disease control rate (DCR) was 100%. The absolute mean decrease in contrast-enhancing disease was 50.7% (95% CI 34.8–66.6). CONCLUSION: NGS for GBM, particularly in the recurrent setting, yields a high rate of actionable alterations. We observed a high ORR and DCR, reflecting the value of NGS when deciding on therapies to match genomic alterations. In conclusion, patient selection and the availability of NGS might impact outcomes in select patients with recurrent GBM.","PeriodicalId":74339,"journal":{"name":"Onco","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45768580","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}
Pub Date : 2021-07-08DOI: 10.21203/RS.3.RS-681014/V1
L. Macharia, Wanjiru Muriithi, D. Nyaga, J. M. Coelho-Aguiar, T. C. Spohr, V. M. Neto
Purpose: Glioblastoma is one of the most aggressive and incurable brain tumors whose progression is driven in part by a small sub population of cells termed as glioblastoma stem cells responsible for the tumor’s low therapy efficacy. Hypoxia, a common phenomenon in glioblastoma also promotes the maintenance and the expansion of the stem cell population whose survival is aided by miRNAs. Methods: GBM stem-like cells cultures were isolated and the relationship between the microenvironments and the in vitro “stemness” of the cells was investigated by evaluating the expression of miRNAs and selected genes. Results: We found miR-128a-3p, 34-5p and 181a-3p to be down-regulated while miR-17-5p and miR-221-3p to be up-regulated in the stem-like cells. When a comparison was made between the stem-like cells cultured under normoxia and hypoxia, a fold down-regulation difference of 3.5 to 5, 2 to 5 and 2 to 4 for miR-34-5p, 128a-3p and 181a-3p was observed respectively and a fold upreulation of 3.5 to 4 and 2.5 to 4 was observed for miR-221-3p and 17-5p respectively. There was an increased expression of HIF-1/2, SOX2, OCT4, VEGF, GLUT-1, BCL2 and survivin under hypoxia. Conclusion: Hypoxia enhanced the expression of several tumor stem cell signature genes, involved in the regulation of stemness, metabolism, angiogenesis and anti-apoptotic property. Most importantly, the miRNA dysregulation in the stem-like cell population adds another layer of gene expression associated with gliomagenesis and maintenance of CSC pointing to new signaling mechanisms whose disruption can be used to successfully target this crucial subpopulation.
{"title":"Evaluation of miRNA Expression in Glioblastoma Stem-like Cells: a Comparison Between Normoxia and Hypoxia Microenvironment","authors":"L. Macharia, Wanjiru Muriithi, D. Nyaga, J. M. Coelho-Aguiar, T. C. Spohr, V. M. Neto","doi":"10.21203/RS.3.RS-681014/V1","DOIUrl":"https://doi.org/10.21203/RS.3.RS-681014/V1","url":null,"abstract":"\u0000 Purpose: Glioblastoma is one of the most aggressive and incurable brain tumors whose progression is driven in part by a small sub population of cells termed as glioblastoma stem cells responsible for the tumor’s low therapy efficacy. Hypoxia, a common phenomenon in glioblastoma also promotes the maintenance and the expansion of the stem cell population whose survival is aided by miRNAs. Methods: GBM stem-like cells cultures were isolated and the relationship between the microenvironments and the in vitro “stemness” of the cells was investigated by evaluating the expression of miRNAs and selected genes. Results: We found miR-128a-3p, 34-5p and 181a-3p to be down-regulated while miR-17-5p and miR-221-3p to be up-regulated in the stem-like cells. When a comparison was made between the stem-like cells cultured under normoxia and hypoxia, a fold down-regulation difference of 3.5 to 5, 2 to 5 and 2 to 4 for miR-34-5p, 128a-3p and 181a-3p was observed respectively and a fold upreulation of 3.5 to 4 and 2.5 to 4 was observed for miR-221-3p and 17-5p respectively. There was an increased expression of HIF-1/2, SOX2, OCT4, VEGF, GLUT-1, BCL2 and survivin under hypoxia. Conclusion: Hypoxia enhanced the expression of several tumor stem cell signature genes, involved in the regulation of stemness, metabolism, angiogenesis and anti-apoptotic property. Most importantly, the miRNA dysregulation in the stem-like cell population adds another layer of gene expression associated with gliomagenesis and maintenance of CSC pointing to new signaling mechanisms whose disruption can be used to successfully target this crucial subpopulation.","PeriodicalId":74339,"journal":{"name":"Onco","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45588257","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}
Anabel Silva, P. Abreu-Mendes, D. Martins, F. Mendes
Bladder cancer (BC) is one of the most common cancers in the world. From an early age, it was observed that chronic inflammation is associated with conditions favorable to the development of tumors, as well as the tumor microenvironment. Moreover, regulating tumor progression also interferes with the therapy’s response. The interaction between the tumor and the immune system led to the development of new immune therapies, the immune checkpoint inhibitors. Immunotherapy has shown a better safety profile, survival, and tolerance compared to standard chemotherapy. This therapy offers an effective alternative to patients who are ineligible for cisplatin and patients with advanced disease progression after platinum-based therapy. The first immunotherapy approved for BC was intravesical instillation with Bacillus Calmette–Guérin, for tumors at early stages. Later, immunotherapy focused on immune checkpoint inhibitors, namely, anti-programmed cell death protein 1 (PD1), anti-programmed cell death protein ligand 1(PD-L1), and anti-antigen 4 associated with cytotoxic T cells (CTLA-4). Currently, five immune checkpoint inhibitors for advanced BC are approved by the Food and Drug Administration (FDA): Atezolizumab, Durvalumab, Avelumab, Pembrolizumab, and Nivolumab. This review addresses the correlation between inflammation, tumor microenvironment, and cancer; various studies regarding immune checkpoint inhibitors, either in monotherapy or in combination therapy, are also addressed.
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