Pub Date : 2019-01-31eCollection Date: 2019-01-01DOI: 10.18632/oncoscience.476
Wenbing Xie, Stephen B Baylin, Hariharan Easwaran
In response to genotoxic stresses, cells are programmed to trigger senescence, involving metabolic slowdown and proliferation arrest, to contain deleterious effects of the damaged genetic material [1]. Two forms of senescence processes are relevant in this context: (a) Replicative Senescence (RS) in response to telomere shortening and/or reactive oxygen species (ROS) that occur during aging; (b) Oncogene Induced Senescence (OIS) in response to oncogenic mutations, such as oncogenic RAS mutations. Failure to trigger senescence can lead to tumorigenesis. Epigenetic alterations play important roles during both senescence and tumor initiation. During senescence, epigenetic alterations play important roles in stably silencing proliferation-promoting genes [2], while in tumorigenesis the epigenetic changes function in suppressing tumor suppressor genes. Here we summarize recent advances in understanding the relation and origins of senescence and tumor epigenomes, and its implications for tumorigenesis.
{"title":"DNA methylation in senescence, aging and cancer.","authors":"Wenbing Xie, Stephen B Baylin, Hariharan Easwaran","doi":"10.18632/oncoscience.476","DOIUrl":"https://doi.org/10.18632/oncoscience.476","url":null,"abstract":"In response to genotoxic stresses, cells are programmed to trigger senescence, involving metabolic slowdown and proliferation arrest, to contain deleterious effects of the damaged genetic material [1]. Two forms of senescence processes are relevant in this context: (a) Replicative Senescence (RS) in response to telomere shortening and/or reactive oxygen species (ROS) that occur during aging; (b) Oncogene Induced Senescence (OIS) in response to oncogenic mutations, such as oncogenic RAS mutations. Failure to trigger senescence can lead to tumorigenesis. Epigenetic alterations play important roles during both senescence and tumor initiation. During senescence, epigenetic alterations play important roles in stably silencing proliferation-promoting genes [2], while in tumorigenesis the epigenetic changes function in suppressing tumor suppressor genes. Here we summarize recent advances in understanding the relation and origins of senescence and tumor epigenomes, and its implications for tumorigenesis.","PeriodicalId":19508,"journal":{"name":"Oncoscience","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.18632/oncoscience.476","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36995715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-01-31eCollection Date: 2019-01-01DOI: 10.18632/oncoscience.474
Michèle Beniey, Takrima Haque, Saima Hassan
{"title":"Translating the role of PARP inhibitors in triple-negative breast cancer.","authors":"Michèle Beniey, Takrima Haque, Saima Hassan","doi":"10.18632/oncoscience.474","DOIUrl":"https://doi.org/10.18632/oncoscience.474","url":null,"abstract":"","PeriodicalId":19508,"journal":{"name":"Oncoscience","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.18632/oncoscience.474","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36995713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-01-31eCollection Date: 2019-01-01DOI: 10.18632/oncoscience.477
Shanthi Ganesh, Bob D Brown, Marc Abrams
{"title":"Direct Inhibition of β-catenin: A new strategy for colorectal cancer.","authors":"Shanthi Ganesh, Bob D Brown, Marc Abrams","doi":"10.18632/oncoscience.477","DOIUrl":"https://doi.org/10.18632/oncoscience.477","url":null,"abstract":"","PeriodicalId":19508,"journal":{"name":"Oncoscience","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6382254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36995716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-01-01DOI: 10.18632/oncoscience.475
Yuriy Loskutov, Elena N Pugacheva
Despite unquestionable progress of the recent decades in cancer therapy and anti-cancer drug discovery, the options for glioblastoma (GBM) patients are very limited. Current standard of care includes aggressive surgical resection, radiation therapy, and chemotherapy, however, majority of patients experience recurrence within 32-36 weeks, and median survival is clenching around 10 months. Clearly, there is a need for new strategies to battle GBM. Unfortunately, with GBM we are not on the solid grounds: there is no known common driver mutation to target; the cell lines, commonly used for GBM research, are obsolete, and their origins are in question; even cells GBM arise from, is a topic of harsh debates. Thus, some guidance system would be highly appreciated, a clue towards which signaling cascades are altered and can be targeted. The primary cilium is a ubiquitous, microtubulebased organelle, an important negative regulator of proliferation and a key sensory organelle. Interestingly, in multiple cancer types, cilia tend to be lost, however, the role of this event is not clear. Modeling the loss of cilia in normal cells suggests that it promotes hyperproliferation in Sonic hedgehog (Shh)-independent cells. In the case of Shh-dependent cell populations such as neural stem cells, ablation of primary cilia seems to inhibit their proliferation and lead to hypocellularity [1]. GBM was reported to have a drastically decreased ciliation rate. Only about 10% of GBM cells assemble cilia. Moreover, electron microscopy analysis of GBM biopsies showed that the few cilia, that they do form, possess multiple structural abnormalities [2]. Further inhibition of primary cilia assembly in patientderived GBM primary cell culture through the introduction of a dominant-negative variant of KIF3A seems to have a minimal and non-coherent effect on both cell proliferation in vitro and tumor growth in the mouse intracranial model [3]. On the other hand, even minimal restoration of primary cilia seems to have a tremendous effect on cell proliferation. This clearly suggests that loss of cilia in GBM is a non-random event, and may be associated with the high proliferative capacity of the tumor cells [4]. It also suggests that GBM are developing either from Shh-independent precursor cells or loose Shh-dependency sometime along with the malignant transformation. Thus, our group focused on investigating the impact of primary cilia loss in astrocytes, speculated to be one of the potential GBM precursor [5]. In concordance with previous observations in other cell types, loss of primary cilia promotes proliferation of astrocytes, however it was not sufficient to cause malignant transformation. Interestingly, general growth factor response, measured by ERK1/2 and AKT activation, was significantly changed upon loss of primary cilia. We traced it down to aberrant lysophosphatidic acid (LPA) signaling: the translocation of lysophosphatidic acid receptor 1 (LPAR1) to the plasma membrane
{"title":"Targeting primary cilia - associated signaling in glioblastoma: guided approach for drug development.","authors":"Yuriy Loskutov, Elena N Pugacheva","doi":"10.18632/oncoscience.475","DOIUrl":"https://doi.org/10.18632/oncoscience.475","url":null,"abstract":"Despite unquestionable progress of the recent decades in cancer therapy and anti-cancer drug discovery, the options for glioblastoma (GBM) patients are very limited. Current standard of care includes aggressive surgical resection, radiation therapy, and chemotherapy, however, majority of patients experience recurrence within 32-36 weeks, and median survival is clenching around 10 months. Clearly, there is a need for new strategies to battle GBM. Unfortunately, with GBM we are not on the solid grounds: there is no known common driver mutation to target; the cell lines, commonly used for GBM research, are obsolete, and their origins are in question; even cells GBM arise from, is a topic of harsh debates. Thus, some guidance system would be highly appreciated, a clue towards which signaling cascades are altered and can be targeted. The primary cilium is a ubiquitous, microtubulebased organelle, an important negative regulator of proliferation and a key sensory organelle. Interestingly, in multiple cancer types, cilia tend to be lost, however, the role of this event is not clear. Modeling the loss of cilia in normal cells suggests that it promotes hyperproliferation in Sonic hedgehog (Shh)-independent cells. In the case of Shh-dependent cell populations such as neural stem cells, ablation of primary cilia seems to inhibit their proliferation and lead to hypocellularity [1]. GBM was reported to have a drastically decreased ciliation rate. Only about 10% of GBM cells assemble cilia. Moreover, electron microscopy analysis of GBM biopsies showed that the few cilia, that they do form, possess multiple structural abnormalities [2]. Further inhibition of primary cilia assembly in patientderived GBM primary cell culture through the introduction of a dominant-negative variant of KIF3A seems to have a minimal and non-coherent effect on both cell proliferation in vitro and tumor growth in the mouse intracranial model [3]. On the other hand, even minimal restoration of primary cilia seems to have a tremendous effect on cell proliferation. This clearly suggests that loss of cilia in GBM is a non-random event, and may be associated with the high proliferative capacity of the tumor cells [4]. It also suggests that GBM are developing either from Shh-independent precursor cells or loose Shh-dependency sometime along with the malignant transformation. Thus, our group focused on investigating the impact of primary cilia loss in astrocytes, speculated to be one of the potential GBM precursor [5]. In concordance with previous observations in other cell types, loss of primary cilia promotes proliferation of astrocytes, however it was not sufficient to cause malignant transformation. Interestingly, general growth factor response, measured by ERK1/2 and AKT activation, was significantly changed upon loss of primary cilia. We traced it down to aberrant lysophosphatidic acid (LPA) signaling: the translocation of lysophosphatidic acid receptor 1 (LPAR1) to the plasma membrane ","PeriodicalId":19508,"journal":{"name":"Oncoscience","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6382257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10384815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-11-09eCollection Date: 2018-09-01DOI: 10.18632/oncoscience.473
Marta Díaz-Martínez, Lucía Benito-Jardón, Lola Alonso, Joaquin Teixidó
{"title":"Reply to: Biological role of miR-204 and miR-211 in melanoma (published in Oncoscience, Vol 5 (7-8), July 2018).","authors":"Marta Díaz-Martínez, Lucía Benito-Jardón, Lola Alonso, Joaquin Teixidó","doi":"10.18632/oncoscience.473","DOIUrl":"https://doi.org/10.18632/oncoscience.473","url":null,"abstract":"","PeriodicalId":19508,"journal":{"name":"Oncoscience","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6231445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36701891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-10-11eCollection Date: 2018-09-01DOI: 10.18632/oncoscience.471
Sachin Kumar Deshmukh, Ajay P Singh, Seema Singh
{"title":"ETV4: an emerging target in pancreatic cancer.","authors":"Sachin Kumar Deshmukh, Ajay P Singh, Seema Singh","doi":"10.18632/oncoscience.471","DOIUrl":"https://doi.org/10.18632/oncoscience.471","url":null,"abstract":"","PeriodicalId":19508,"journal":{"name":"Oncoscience","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6231443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36701890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-10-11eCollection Date: 2018-09-01DOI: 10.18632/oncoscience.472
Dana C Galván, Anoop P Ayyappan, Brad A Bryan
Angiosarcoma is the most common malignant cardiac tumor. Cardiac angiosarcoma is a highly lethal neoplasm that is largely resistant to conventional anti-cancer therapy. Mean survival of patients with cardiac angiosarcoma is only 4 months, and almost all patients will succumb to the disease within 1 year. The beta blocker propranolol is an emerging therapy against angiosarcoma. When combined with conventional therapies, propranolol increases progression free and overall survival in patients with this tumor type. It is currently unknown if propranolol is capable of showing anti-cancer efficacy as a single agent therapy. We report a case of a 61 year old woman diagnosed with primary cardiac angiosarcoma and liver and lung metastases. This patient chose to decline conventional therapy, and instead was prescribed the beta blocker propranolol as a single agent treatment. After 12 months, the mediastinal mass substantially debulked and decreased in size, and the metastatic nodules stabilized or resolved with no evidence of hyper-metabolic activity on PET-CT. This is the first reported data showing long term efficacy of the beta blocker propranolol as a single agent therapy against angiosarcoma.
{"title":"Regression of primary cardiac angiosarcoma and metastatic nodules following propranolol as a single agent treatment.","authors":"Dana C Galván, Anoop P Ayyappan, Brad A Bryan","doi":"10.18632/oncoscience.472","DOIUrl":"https://doi.org/10.18632/oncoscience.472","url":null,"abstract":"<p><p>Angiosarcoma is the most common malignant cardiac tumor. Cardiac angiosarcoma is a highly lethal neoplasm that is largely resistant to conventional anti-cancer therapy. Mean survival of patients with cardiac angiosarcoma is only 4 months, and almost all patients will succumb to the disease within 1 year. The beta blocker propranolol is an emerging therapy against angiosarcoma. When combined with conventional therapies, propranolol increases progression free and overall survival in patients with this tumor type. It is currently unknown if propranolol is capable of showing anti-cancer efficacy as a single agent therapy. We report a case of a 61 year old woman diagnosed with primary cardiac angiosarcoma and liver and lung metastases. This patient chose to decline conventional therapy, and instead was prescribed the beta blocker propranolol as a single agent treatment. After 12 months, the mediastinal mass substantially debulked and decreased in size, and the metastatic nodules stabilized or resolved with no evidence of hyper-metabolic activity on PET-CT. This is the first reported data showing long term efficacy of the beta blocker propranolol as a single agent therapy against angiosarcoma.</p>","PeriodicalId":19508,"journal":{"name":"Oncoscience","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6231448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36701892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-08-28eCollection Date: 2018-11-01DOI: 10.18632/oncoscience.469
Thu H Truong, Carol A Lange, Julie H Ostrander
{"title":"Targeting steroid receptor co-activators to inhibit breast cancer stem cells.","authors":"Thu H Truong, Carol A Lange, Julie H Ostrander","doi":"10.18632/oncoscience.469","DOIUrl":"https://doi.org/10.18632/oncoscience.469","url":null,"abstract":"","PeriodicalId":19508,"journal":{"name":"Oncoscience","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6326735/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36915155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-08-28eCollection Date: 2018-11-01DOI: 10.18632/oncoscience.467
Elisa Ventura, Francesca Pentimalli, Antonio Giordano
{"title":"RBL2/p130: a direct AKT substrate and mediator of AKT inhibition-induced apoptosis.","authors":"Elisa Ventura, Francesca Pentimalli, Antonio Giordano","doi":"10.18632/oncoscience.467","DOIUrl":"https://doi.org/10.18632/oncoscience.467","url":null,"abstract":"","PeriodicalId":19508,"journal":{"name":"Oncoscience","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6326738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36915154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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