{"title":"PARP inhibitors beyond BRCA-mutated cancers: precision medicine at the crossroads","authors":"B. Tomasik, M. Bienkowski, J. Jassem","doi":"10.21037/PCM-21-8","DOIUrl":"https://doi.org/10.21037/PCM-21-8","url":null,"abstract":"","PeriodicalId":74487,"journal":{"name":"Precision cancer medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43671739","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}
C. Ordóñez-Reyes, A. Ruíz-Patiño, O. Arrieta, L. Zatarain-Barrón, L. Rojas, G. Recondo, L. Ricaurte, A. Cardona
: Non-small cell lung cancer (NSCLC) is responsible of 85% of lung cancer (LC) cases. Therefore, epithelial growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) were developed and have improved clinical outcomes of EGFR -mutant NSCLC patients. However, these patients inevitably develop resistance to those medications. Some of the resistance mechanisms are T790M mutation and transformation of lung adenocarcinoma to small cell lung cancer (SCLC). Conversely, only a few EGFR -mutant NSCLC cases reported a long-term survival of more than 5 years. The present case concerns a 53-year-old never smoker woman of Hispanic origin, that debuted with dry cough without dyspnea and intermittent high-intensity pain in the left chest and spine. She was diagnosed with metastatic NSCLC and started treatment with platinum-based chemotherapy double. After an EGFR -mutation was identified, the patient started target therapy. Over the years, treatment was escalated because of the resistance she developed against TKIs. T790M resistance mutation was reported and persisted over time; additionally the appearance of TP53 R213 mutation was found years later. Treatment with osimertinib was successfully administered for 10 months and after that meningeal progression was found. At the same time, transdifferentiation to SCLC was confirmed by histological analysis. Carboplatin/etoposide/osimertinib was then unsuccessfully administered. The patient died in January 2020, after 12.5 years of overall survival (OS) and 10 lines of treatment. To our knowledge, this article presents one of the longest reported survivals of a metastatic LC patient with EGFR mutation. 12
{"title":"Precision oncology in EGFR positive non-small cell lung cancer: breaking the 10-year barrier—a case report","authors":"C. Ordóñez-Reyes, A. Ruíz-Patiño, O. Arrieta, L. Zatarain-Barrón, L. Rojas, G. Recondo, L. Ricaurte, A. Cardona","doi":"10.21037/PCM-20-53","DOIUrl":"https://doi.org/10.21037/PCM-20-53","url":null,"abstract":": Non-small cell lung cancer (NSCLC) is responsible of 85% of lung cancer (LC) cases. Therefore, epithelial growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) were developed and have improved clinical outcomes of EGFR -mutant NSCLC patients. However, these patients inevitably develop resistance to those medications. Some of the resistance mechanisms are T790M mutation and transformation of lung adenocarcinoma to small cell lung cancer (SCLC). Conversely, only a few EGFR -mutant NSCLC cases reported a long-term survival of more than 5 years. The present case concerns a 53-year-old never smoker woman of Hispanic origin, that debuted with dry cough without dyspnea and intermittent high-intensity pain in the left chest and spine. She was diagnosed with metastatic NSCLC and started treatment with platinum-based chemotherapy double. After an EGFR -mutation was identified, the patient started target therapy. Over the years, treatment was escalated because of the resistance she developed against TKIs. T790M resistance mutation was reported and persisted over time; additionally the appearance of TP53 R213 mutation was found years later. Treatment with osimertinib was successfully administered for 10 months and after that meningeal progression was found. At the same time, transdifferentiation to SCLC was confirmed by histological analysis. Carboplatin/etoposide/osimertinib was then unsuccessfully administered. The patient died in January 2020, after 12.5 years of overall survival (OS) and 10 lines of treatment. To our knowledge, this article presents one of the longest reported survivals of a metastatic LC patient with EGFR mutation. 12","PeriodicalId":74487,"journal":{"name":"Precision cancer medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44009623","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}
Background: There is increasing need to develop targeted therapies for triple negative breast cancer (TNBC) as conventional therapies are ineffective at combatting systemic disease. Triple negative breast tumors often have increased expression of receptor tyrosine kinases (RTKs) such as epidermal growth factor receptor (EGFR) and the hepatocyte growth factor receptor c-Met; presenting as potential targets for treatment. However, targeted anti-EGFR and anti-c-Met therapies have faced mixed results in clinical trials due to acquired resistance. In this study, we explore the potential of EGFR and c-Met as potential targets for treatment of metastatic TNBC, including assessment of potential mechanisms of response. Methods: To help define the clinical context, we first evaluated EGFR and c-Met expression data from The Cancer Genome Atlas (TCGA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC). Using MDA-MB-468 and MDA-MB-231 TNBC cell lines, we also investigated the effects of the c-Met inhibitor cabozantinib and the EGFR inhibitor erlotinib on in vitro cell proliferation, migration, invasion and downstream signaling pathways. Results: TCGA and CPTAC data demonstrated increased expression of both EGFR and c-Met in patients with TNBC relative to other breast cancer subtypes (P<0.05). We observed that MDA-MB-468 cells were more sensitive to the anti-proliferative effects of erlotinib (IC50 =9.70 nM) compared to MDA-MB-231 cells (IC50 =5.48 μM), whereas MDA-MB-231 cells were more sensitive to cabozantinib (IC50 =1.68 μM) than MDA-MB-468 cells (IC50 =8.89 μM). In erlotinib-treated MDA-MB-468 cells, we observed a decrease in both phosphorylated EGFR (Y1086) and total EGFR as well as decreased activation of ERK1/2 (T202, Y204) (P<0.05). Cabozantinib, although not directly affecting the activation of c-Met, attenuated activation of AKT1 (S473) in MDA-MB-231 cells (P<0.05). Finally, we observed a reduction in cell migration and invasion of erlotinib-treated MDA-MB-468 cells and cabozantinib-treated MDA-MB-231 cells compared to controls (P<0.05). Conclusions: Erlotinib and cabozantinib have varying anti-proliferative and anti-migratory effects in different TNBC models. Elucidation of the underlying mechanisms that define the heterogenous response to tyrosine kinase inhibitors (TKIs) in TNBC could help identify biomarkers to stratify patients for treatment and/or facilitate discovery of targets to attenuate acquired resistance.
{"title":"Anti-proliferative and anti-migratory effects of EGFR and c-Met tyrosine kinase inhibitors in triple negative breast cancer cells","authors":"Cory Lefebvre, A. Allan","doi":"10.21037/PCM-20-62","DOIUrl":"https://doi.org/10.21037/PCM-20-62","url":null,"abstract":"Background: There is increasing need to develop targeted therapies for triple negative breast cancer (TNBC) as conventional therapies are ineffective at combatting systemic disease. Triple negative breast tumors often have increased expression of receptor tyrosine kinases (RTKs) such as epidermal growth factor receptor (EGFR) and the hepatocyte growth factor receptor c-Met; presenting as potential targets for treatment. However, targeted anti-EGFR and anti-c-Met therapies have faced mixed results in clinical trials due to acquired resistance. In this study, we explore the potential of EGFR and c-Met as potential targets for treatment of metastatic TNBC, including assessment of potential mechanisms of response. Methods: To help define the clinical context, we first evaluated EGFR and c-Met expression data from The Cancer Genome Atlas (TCGA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC). Using MDA-MB-468 and MDA-MB-231 TNBC cell lines, we also investigated the effects of the c-Met inhibitor cabozantinib and the EGFR inhibitor erlotinib on in vitro cell proliferation, migration, invasion and downstream signaling pathways. Results: TCGA and CPTAC data demonstrated increased expression of both EGFR and c-Met in patients with TNBC relative to other breast cancer subtypes (P<0.05). We observed that MDA-MB-468 cells were more sensitive to the anti-proliferative effects of erlotinib (IC50 =9.70 nM) compared to MDA-MB-231 cells (IC50 =5.48 μM), whereas MDA-MB-231 cells were more sensitive to cabozantinib (IC50 =1.68 μM) than MDA-MB-468 cells (IC50 =8.89 μM). In erlotinib-treated MDA-MB-468 cells, we observed a decrease in both phosphorylated EGFR (Y1086) and total EGFR as well as decreased activation of ERK1/2 (T202, Y204) (P<0.05). Cabozantinib, although not directly affecting the activation of c-Met, attenuated activation of AKT1 (S473) in MDA-MB-231 cells (P<0.05). Finally, we observed a reduction in cell migration and invasion of erlotinib-treated MDA-MB-468 cells and cabozantinib-treated MDA-MB-231 cells compared to controls (P<0.05). Conclusions: Erlotinib and cabozantinib have varying anti-proliferative and anti-migratory effects in different TNBC models. Elucidation of the underlying mechanisms that define the heterogenous response to tyrosine kinase inhibitors (TKIs) in TNBC could help identify biomarkers to stratify patients for treatment and/or facilitate discovery of targets to attenuate acquired resistance.","PeriodicalId":74487,"journal":{"name":"Precision cancer medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48113930","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 : 2021-02-22DOI: 10.21037/PCM-2020-LCIW-01
M. Casiraghi, L. Spaggiari
{"title":"Lung cancer screening: think pink!","authors":"M. Casiraghi, L. Spaggiari","doi":"10.21037/PCM-2020-LCIW-01","DOIUrl":"https://doi.org/10.21037/PCM-2020-LCIW-01","url":null,"abstract":"","PeriodicalId":74487,"journal":{"name":"Precision cancer medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45400125","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}
F. Parisi, G. Rossi, F. Biello, M. Tagliamento, G. Barletta, L. Zullo, E. Cella, G. Sacco, C. Dellepiane, E. Bennicelli, D. Favero, A. Alama, S. Coco, S. Marconi, L. Zinoli, E. Tanda, P. Pronzato, E. Rijavec, C. Genova
Background and Objective: Strategies for diagnosis and treatment of oncogene-addicted non-small cell lung cancer (NSCLC) are constantly evolving. In particular, the development of novel techniques for the molecular classification of NSCLC lead to detect many molecular aberrations of therapeutic interest, even in peripheral blood, including ROS proto-oncogene 1, receptor tyrosine kinase, encoded by ROS1 gene. Currently there are few drugs targeting ROS1 and most of available data on their activity comes from non-randomized studies, considering the low incidence of ROS1 alterations. Only three drugs are registered for FDA (crizotinib, entrectinib and ceritinib), with similar safety profile; no study comparing these two drugs is available yet. Methods: This narrative review was conducted by gathering all the relevant literature in PubMed from 2007 to 2021 on evolving techniques for the molecular detection of ROS1 rearrangements and also on main mechanisms of resistance with consequent developments of more selective drugs. Research was carried out at both preclinical and clinical levels. For the preclinical part, we selected more than 50 publications on the implications of in situ laboratory and molecular biology techniques comparing these approaches; for the clinical part we collected the main publications on ROS1 rearranged oncogene-addicted NSCLC and reported international guidelines. We included data from ten phase I/II trials testing efficacy and safety of TKIs targeting ROS1 rearrangement. rearrangements and the consequent therapeutic implication in lung cancer. To this aim, we have analysed all the relevant literature in PubMed from 2007 to 2021 on evolving techniques for the molecular detection of ROS1 rearrangements and on the main mechanisms of resistance with consequent developments of more selective drugs ( Table 1 ). The PubMed database was searched principally using the keywords “Non-small cell lung cancer”, “ ROS1 rearrangements”. We excluded articles not published in English. Research was performed at both preclinical and clinical levels. For the preclinical part, we selected more than 50 publications on the implications of in situ laboratory and molecular biology techniques comparing these approaches; for the clinical part we collected the main publications on ROS1 rearranged oncogene-addicted NSCLCs and reported international guidelines. We included data from ten phase I/II trials testing efficacy and safety of TKIs targeting ROS1 rearrangement. despite the rarity of this molecular alteration, have reached important developments. The contribution of this review would be to explore the main developments on the diagnosis of ROS1 rearrangements and to identify therapeutic opportunities both those currently available in clinical practice and those not currently available but promising for the near future.
{"title":"Current state of the art on the diagnosis and the role of target therapy for treatment of ROS1-rearranged non-small cell lung cancer: a narrative review","authors":"F. Parisi, G. Rossi, F. Biello, M. Tagliamento, G. Barletta, L. Zullo, E. Cella, G. Sacco, C. Dellepiane, E. Bennicelli, D. Favero, A. Alama, S. Coco, S. Marconi, L. Zinoli, E. Tanda, P. Pronzato, E. Rijavec, C. Genova","doi":"10.21037/pcm-22-6","DOIUrl":"https://doi.org/10.21037/pcm-22-6","url":null,"abstract":"Background and Objective: Strategies for diagnosis and treatment of oncogene-addicted non-small cell lung cancer (NSCLC) are constantly evolving. In particular, the development of novel techniques for the molecular classification of NSCLC lead to detect many molecular aberrations of therapeutic interest, even in peripheral blood, including ROS proto-oncogene 1, receptor tyrosine kinase, encoded by ROS1 gene. Currently there are few drugs targeting ROS1 and most of available data on their activity comes from non-randomized studies, considering the low incidence of ROS1 alterations. Only three drugs are registered for FDA (crizotinib, entrectinib and ceritinib), with similar safety profile; no study comparing these two drugs is available yet. Methods: This narrative review was conducted by gathering all the relevant literature in PubMed from 2007 to 2021 on evolving techniques for the molecular detection of ROS1 rearrangements and also on main mechanisms of resistance with consequent developments of more selective drugs. Research was carried out at both preclinical and clinical levels. For the preclinical part, we selected more than 50 publications on the implications of in situ laboratory and molecular biology techniques comparing these approaches; for the clinical part we collected the main publications on ROS1 rearranged oncogene-addicted NSCLC and reported international guidelines. We included data from ten phase I/II trials testing efficacy and safety of TKIs targeting ROS1 rearrangement. rearrangements and the consequent therapeutic implication in lung cancer. To this aim, we have analysed all the relevant literature in PubMed from 2007 to 2021 on evolving techniques for the molecular detection of ROS1 rearrangements and on the main mechanisms of resistance with consequent developments of more selective drugs ( Table 1 ). The PubMed database was searched principally using the keywords “Non-small cell lung cancer”, “ ROS1 rearrangements”. We excluded articles not published in English. Research was performed at both preclinical and clinical levels. For the preclinical part, we selected more than 50 publications on the implications of in situ laboratory and molecular biology techniques comparing these approaches; for the clinical part we collected the main publications on ROS1 rearranged oncogene-addicted NSCLCs and reported international guidelines. We included data from ten phase I/II trials testing efficacy and safety of TKIs targeting ROS1 rearrangement. despite the rarity of this molecular alteration, have reached important developments. The contribution of this review would be to explore the main developments on the diagnosis of ROS1 rearrangements and to identify therapeutic opportunities both those currently available in clinical practice and those not currently available but promising for the near future.","PeriodicalId":74487,"journal":{"name":"Precision cancer medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42890392","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}
Zezhou Wang, Sanjian Yu, Xiaoshuang Feng, Xia Qiu, Hui Ji, Hailin Shan, Qing Shao, Heng Xia, Feng Cao, Jun Li, Cuixia Fu, Liqin Chen, Xiaona Lu, Tingting Su, Qian-qian Yu, Shengqun Hou, Honglian Wang, Yunyong Liu, Ying Zheng, Z. Shao, Zhen Hu
{"title":"Protocol: screening of genetic susceptibility genes for breast cancer patients and establishment of genetic high-risk populations cohort in east china communities","authors":"Zezhou Wang, Sanjian Yu, Xiaoshuang Feng, Xia Qiu, Hui Ji, Hailin Shan, Qing Shao, Heng Xia, Feng Cao, Jun Li, Cuixia Fu, Liqin Chen, Xiaona Lu, Tingting Su, Qian-qian Yu, Shengqun Hou, Honglian Wang, Yunyong Liu, Ying Zheng, Z. Shao, Zhen Hu","doi":"10.21037/pcm-22-36","DOIUrl":"https://doi.org/10.21037/pcm-22-36","url":null,"abstract":"","PeriodicalId":74487,"journal":{"name":"Precision cancer medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43505995","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":"Review: biological implications of oncogenic rearrangements in non-small cell lung cancer","authors":"M. D. Di Marco, C. Voena","doi":"10.21037/pcm-22-7","DOIUrl":"https://doi.org/10.21037/pcm-22-7","url":null,"abstract":"","PeriodicalId":74487,"journal":{"name":"Precision cancer medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44265877","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}
E. Lai, M. Persano, M. Dubois, D. Spanu, C. Donisi, M. Pozzari, G. Deias, G. Saba, M. Migliari, N. Liscia, M. Dessì, M. Scartozzi, F. Atzori
{"title":"Drug-related toxicity in breast cancer patients: a new path towards tailored treatment?—A narrative review","authors":"E. Lai, M. Persano, M. Dubois, D. Spanu, C. Donisi, M. Pozzari, G. Deias, G. Saba, M. Migliari, N. Liscia, M. Dessì, M. Scartozzi, F. Atzori","doi":"10.21037/pcm-21-38","DOIUrl":"https://doi.org/10.21037/pcm-21-38","url":null,"abstract":"","PeriodicalId":74487,"journal":{"name":"Precision cancer medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41683996","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 mesothelioma is a rare but rapidly fatal disease highly enriched for innate immunity signature in a subset of patients with better clinical outcome. We provide here an overview of current knowledge on RNA regulatory networks altered in mesothelioma and resulting in increased expression of non-coding-RNA ligands stimulating the innate immune system. The focus on non-coding RNA (ncRNA) ligands is dictated by the fact that a large fraction of the non-coding genome is known to be transcribed and forms duplex RNAs able to stimulate anti-viral defense. Hence, we mostly describe double-stranded RNA sensors such as cytosolic RIG-I-like receptors and endosomal leucine-rich receptors Toll-like receptors 3 and their endogenous ligands. The latter include products downstream alteration of alternative splicing, altered RNA processing or expression of repetitive elements induced by demethylation events or deficiency of chromatin remodelers such as histone methyltransferase SETDB1 or histone demethylase KDM1A/LSD1 or inhibition of CDK4/6. Based on knowledge acquired either in experimental pre-clinical models or in clinical trials in other cancers types, all these events are likely to influence the outcome of mesothelioma patients treatment with new modalities which are explored in current mesothelioma clinical trials. Furthermore, immune checkpoint inhibition became recently standard of care in unresectable mesothelioma. Abstract: Malignant mesothelioma is a rare but rapidly fatal disease highly enriched for innate immunity signature in a subset of patients with better clinical outcome. We provide here an overview of current knowledge on RNA regulatory networks altered in mesothelioma and resulting in increased expression of non-coding-RNA ligands stimulating the innate immune system. The focus on non-coding RNA (ncRNA) ligands is dictated by the fact that a large fraction of the non-coding genome is known to be transcribed and forms duplex RNAs able to stimulate anti-viral defense. Hence, we mostly describe double-stranded RNA sensors such as cytosolic RIG-I-like receptors and endosomal leucine-rich receptors Toll-like receptors 3 and their endogenous ligands. The latter include products downstream alteration of alternative splicing, altered RNA processing or expression of repetitive elements induced by demethylation events or deficiency of chromatin remodelers such as histone methyltransferase SETDB1 or histone demethylase KDM1A/LSD1 or inhibition of CDK4/6. Based on knowledge acquired either in experimental pre-clinical models or in clinical trials in other cancers types, all these events are likely to influence the outcome of mesothelioma patients treatment with new modalities which are explored in current mesothelioma clinical trials. Furthermore, immune checkpoint inhibition became recently standard of care in unresectable mesothelioma. IFN -β (TRIF). TRIF TBK1-dependent receptor-interacting serine/threonine-protein kinase 3-dependent Nucleic
{"title":"Non-coding RNA regulatory networks in mesothelioma: a narrative review of their implication in innate immune signaling pathways","authors":"E. Felley-Bosco","doi":"10.21037/pcm-21-4","DOIUrl":"https://doi.org/10.21037/pcm-21-4","url":null,"abstract":": Malignant mesothelioma is a rare but rapidly fatal disease highly enriched for innate immunity signature in a subset of patients with better clinical outcome. We provide here an overview of current knowledge on RNA regulatory networks altered in mesothelioma and resulting in increased expression of non-coding-RNA ligands stimulating the innate immune system. The focus on non-coding RNA (ncRNA) ligands is dictated by the fact that a large fraction of the non-coding genome is known to be transcribed and forms duplex RNAs able to stimulate anti-viral defense. Hence, we mostly describe double-stranded RNA sensors such as cytosolic RIG-I-like receptors and endosomal leucine-rich receptors Toll-like receptors 3 and their endogenous ligands. The latter include products downstream alteration of alternative splicing, altered RNA processing or expression of repetitive elements induced by demethylation events or deficiency of chromatin remodelers such as histone methyltransferase SETDB1 or histone demethylase KDM1A/LSD1 or inhibition of CDK4/6. Based on knowledge acquired either in experimental pre-clinical models or in clinical trials in other cancers types, all these events are likely to influence the outcome of mesothelioma patients treatment with new modalities which are explored in current mesothelioma clinical trials. Furthermore, immune checkpoint inhibition became recently standard of care in unresectable mesothelioma. Abstract: Malignant mesothelioma is a rare but rapidly fatal disease highly enriched for innate immunity signature in a subset of patients with better clinical outcome. We provide here an overview of current knowledge on RNA regulatory networks altered in mesothelioma and resulting in increased expression of non-coding-RNA ligands stimulating the innate immune system. The focus on non-coding RNA (ncRNA) ligands is dictated by the fact that a large fraction of the non-coding genome is known to be transcribed and forms duplex RNAs able to stimulate anti-viral defense. Hence, we mostly describe double-stranded RNA sensors such as cytosolic RIG-I-like receptors and endosomal leucine-rich receptors Toll-like receptors 3 and their endogenous ligands. The latter include products downstream alteration of alternative splicing, altered RNA processing or expression of repetitive elements induced by demethylation events or deficiency of chromatin remodelers such as histone methyltransferase SETDB1 or histone demethylase KDM1A/LSD1 or inhibition of CDK4/6. Based on knowledge acquired either in experimental pre-clinical models or in clinical trials in other cancers types, all these events are likely to influence the outcome of mesothelioma patients treatment with new modalities which are explored in current mesothelioma clinical trials. Furthermore, immune checkpoint inhibition became recently standard of care in unresectable mesothelioma. IFN -β (TRIF). TRIF TBK1-dependent receptor-interacting serine/threonine-protein kinase 3-dependent Nucleic ","PeriodicalId":74487,"journal":{"name":"Precision cancer medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45970973","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}
Z. Wang, Glauco Lorenzut, Zhen Zhang, A. Dekker, A. Traverso
{"title":"Applications of generative adversarial networks (GANs) in radiotherapy: narrative review","authors":"Z. Wang, Glauco Lorenzut, Zhen Zhang, A. Dekker, A. Traverso","doi":"10.21037/pcm-22-28","DOIUrl":"https://doi.org/10.21037/pcm-22-28","url":null,"abstract":"","PeriodicalId":74487,"journal":{"name":"Precision cancer medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46434741","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}
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