@article{RN6068,
   author = {Kim, Y. and Varn, F. S. and Park, S. H. and Yoon, B. W. and Park, H. R. and Lee, C. and Verhaak, R. G. W. and Paek, S. H.},
   title = {Perspective of mesenchymal transformation in glioblastoma},
   journal = {Acta Neuropathol Commun},
   volume = {9},
   number = {1},
   pages = {50},
   note = {2051-5960
Kim, Yona
Varn, Frederick S
Park, Sung-Hye
Yoon, Byung Woo
Park, Hye Ran
Lee, Charles
Verhaak, Roel G W
Paek, Sun Ha
Orcid: 0000-0003-3007-8653
Journal Article
Research Support, Non-U.S. Gov't
Review
England
2021/03/26
Acta Neuropathol Commun. 2021 Mar 24;9(1):50. doi: 10.1186/s40478-021-01151-4.},
   abstract = {Despite aggressive multimodal treatment, glioblastoma (GBM), a grade IV primary brain tumor, still portends a poor prognosis with a median overall survival of 12-16 months. The complexity of GBM treatment mainly lies in the inter- and intra-tumoral heterogeneity, which largely contributes to the treatment-refractory and recurrent nature of GBM. By paving the road towards the development of personalized medicine for GBM patients, the cancer genome atlas classification scheme of GBM into distinct transcriptional subtypes has been considered an invaluable approach to overcoming this heterogeneity. Among the identified transcriptional subtypes, the mesenchymal subtype has been found associated with more aggressive, invasive, angiogenic, hypoxic, necrotic, inflammatory, and multitherapy-resistant features than other transcriptional subtypes. Accordingly, mesenchymal GBM patients were found to exhibit worse prognosis than other subtypes when patients with high transcriptional heterogeneity were excluded. Furthermore, identification of the master mesenchymal regulators and their downstream signaling pathways has not only increased our understanding of the complex regulatory transcriptional networks of mesenchymal GBM, but also has generated a list of potent inhibitors for clinical trials. Importantly, the mesenchymal transition of GBM has been found to be tightly associated with treatment-induced phenotypic changes in recurrence. Together, these findings indicate that elucidating the governing and plastic transcriptomic natures of mesenchymal GBM is critical in order to develop novel and selective therapeutic strategies that can improve both patient care and clinical outcomes. Thus, the focus of our review will be on the recent advances in the understanding of the transcriptome of mesenchymal GBM and discuss microenvironmental, metabolic, and treatment-related factors as critical components through which the mesenchymal signature may be acquired. We also take into consideration the transcriptomic plasticity of GBM to discuss the future perspectives in employing selective therapeutic strategies against mesenchymal GBM.},
   keywords = {Brain Neoplasms/*genetics/*pathology
Epithelial-Mesenchymal Transition/*genetics
Glioblastoma/*genetics/*pathology
Humans
Glioblastoma
Master transcriptional regulator
Mesenchymal transition
TAMs
Transcriptomic plasticity},
   ISSN = {2051-5960},
   DOI = {10.1186/s40478-021-01151-4},
   year = {2021},
   type = {Journal Article}
}

{"_id":"aMfTYyxS9NfiPFxnK","bibbaseid":"kim-varn-park-yoon-park-lee-verhaak-paek-perspectiveofmesenchymaltransformationinglioblastoma-2021","author_short":["Kim, Y.","Varn, F. S.","Park, S. H.","Yoon, B. W.","Park, H. R.","Lee, C.","Verhaak, R. G. W.","Paek, S. H."],"bibdata":{"bibtype":"article","type":"Journal Article","author":[{"propositions":[],"lastnames":["Kim"],"firstnames":["Y."],"suffixes":[]},{"propositions":[],"lastnames":["Varn"],"firstnames":["F.","S."],"suffixes":[]},{"propositions":[],"lastnames":["Park"],"firstnames":["S.","H."],"suffixes":[]},{"propositions":[],"lastnames":["Yoon"],"firstnames":["B.","W."],"suffixes":[]},{"propositions":[],"lastnames":["Park"],"firstnames":["H.","R."],"suffixes":[]},{"propositions":[],"lastnames":["Lee"],"firstnames":["C."],"suffixes":[]},{"propositions":[],"lastnames":["Verhaak"],"firstnames":["R.","G.","W."],"suffixes":[]},{"propositions":[],"lastnames":["Paek"],"firstnames":["S.","H."],"suffixes":[]}],"title":"Perspective of mesenchymal transformation in glioblastoma","journal":"Acta Neuropathol Commun","volume":"9","number":"1","pages":"50","note":"2051-5960 Kim, Yona Varn, Frederick S Park, Sung-Hye Yoon, Byung Woo Park, Hye Ran Lee, Charles Verhaak, Roel G W Paek, Sun Ha Orcid: 0000-0003-3007-8653 Journal Article Research Support, Non-U.S. Gov't Review England 2021/03/26 Acta Neuropathol Commun. 2021 Mar 24;9(1):50. doi: 10.1186/s40478-021-01151-4.","abstract":"Despite aggressive multimodal treatment, glioblastoma (GBM), a grade IV primary brain tumor, still portends a poor prognosis with a median overall survival of 12-16 months. The complexity of GBM treatment mainly lies in the inter- and intra-tumoral heterogeneity, which largely contributes to the treatment-refractory and recurrent nature of GBM. By paving the road towards the development of personalized medicine for GBM patients, the cancer genome atlas classification scheme of GBM into distinct transcriptional subtypes has been considered an invaluable approach to overcoming this heterogeneity. Among the identified transcriptional subtypes, the mesenchymal subtype has been found associated with more aggressive, invasive, angiogenic, hypoxic, necrotic, inflammatory, and multitherapy-resistant features than other transcriptional subtypes. Accordingly, mesenchymal GBM patients were found to exhibit worse prognosis than other subtypes when patients with high transcriptional heterogeneity were excluded. Furthermore, identification of the master mesenchymal regulators and their downstream signaling pathways has not only increased our understanding of the complex regulatory transcriptional networks of mesenchymal GBM, but also has generated a list of potent inhibitors for clinical trials. Importantly, the mesenchymal transition of GBM has been found to be tightly associated with treatment-induced phenotypic changes in recurrence. Together, these findings indicate that elucidating the governing and plastic transcriptomic natures of mesenchymal GBM is critical in order to develop novel and selective therapeutic strategies that can improve both patient care and clinical outcomes. Thus, the focus of our review will be on the recent advances in the understanding of the transcriptome of mesenchymal GBM and discuss microenvironmental, metabolic, and treatment-related factors as critical components through which the mesenchymal signature may be acquired. We also take into consideration the transcriptomic plasticity of GBM to discuss the future perspectives in employing selective therapeutic strategies against mesenchymal GBM.","keywords":"Brain Neoplasms/*genetics/*pathology Epithelial-Mesenchymal Transition/*genetics Glioblastoma/*genetics/*pathology Humans Glioblastoma Master transcriptional regulator Mesenchymal transition TAMs Transcriptomic plasticity","issn":"2051-5960","doi":"10.1186/s40478-021-01151-4","year":"2021","bibtex":"@article{RN6068,\n author = {Kim, Y. and Varn, F. S. and Park, S. H. and Yoon, B. W. and Park, H. R. and Lee, C. and Verhaak, R. G. W. and Paek, S. H.},\n title = {Perspective of mesenchymal transformation in glioblastoma},\n journal = {Acta Neuropathol Commun},\n volume = {9},\n number = {1},\n pages = {50},\n note = {2051-5960\nKim, Yona\nVarn, Frederick S\nPark, Sung-Hye\nYoon, Byung Woo\nPark, Hye Ran\nLee, Charles\nVerhaak, Roel G W\nPaek, Sun Ha\nOrcid: 0000-0003-3007-8653\nJournal Article\nResearch Support, Non-U.S. Gov't\nReview\nEngland\n2021/03/26\nActa Neuropathol Commun. 2021 Mar 24;9(1):50. doi: 10.1186/s40478-021-01151-4.},\n abstract = {Despite aggressive multimodal treatment, glioblastoma (GBM), a grade IV primary brain tumor, still portends a poor prognosis with a median overall survival of 12-16 months. The complexity of GBM treatment mainly lies in the inter- and intra-tumoral heterogeneity, which largely contributes to the treatment-refractory and recurrent nature of GBM. By paving the road towards the development of personalized medicine for GBM patients, the cancer genome atlas classification scheme of GBM into distinct transcriptional subtypes has been considered an invaluable approach to overcoming this heterogeneity. Among the identified transcriptional subtypes, the mesenchymal subtype has been found associated with more aggressive, invasive, angiogenic, hypoxic, necrotic, inflammatory, and multitherapy-resistant features than other transcriptional subtypes. Accordingly, mesenchymal GBM patients were found to exhibit worse prognosis than other subtypes when patients with high transcriptional heterogeneity were excluded. Furthermore, identification of the master mesenchymal regulators and their downstream signaling pathways has not only increased our understanding of the complex regulatory transcriptional networks of mesenchymal GBM, but also has generated a list of potent inhibitors for clinical trials. Importantly, the mesenchymal transition of GBM has been found to be tightly associated with treatment-induced phenotypic changes in recurrence. Together, these findings indicate that elucidating the governing and plastic transcriptomic natures of mesenchymal GBM is critical in order to develop novel and selective therapeutic strategies that can improve both patient care and clinical outcomes. Thus, the focus of our review will be on the recent advances in the understanding of the transcriptome of mesenchymal GBM and discuss microenvironmental, metabolic, and treatment-related factors as critical components through which the mesenchymal signature may be acquired. We also take into consideration the transcriptomic plasticity of GBM to discuss the future perspectives in employing selective therapeutic strategies against mesenchymal GBM.},\n keywords = {Brain Neoplasms/*genetics/*pathology\nEpithelial-Mesenchymal Transition/*genetics\nGlioblastoma/*genetics/*pathology\nHumans\nGlioblastoma\nMaster transcriptional regulator\nMesenchymal transition\nTAMs\nTranscriptomic plasticity},\n ISSN = {2051-5960},\n DOI = {10.1186/s40478-021-01151-4},\n year = {2021},\n type = {Journal Article}\n}\n\n","author_short":["Kim, Y.","Varn, F. S.","Park, S. H.","Yoon, B. W.","Park, H. R.","Lee, C.","Verhaak, R. G. W.","Paek, S. H."],"key":"RN6068","id":"RN6068","bibbaseid":"kim-varn-park-yoon-park-lee-verhaak-paek-perspectiveofmesenchymaltransformationinglioblastoma-2021","role":"author","urls":{},"keyword":["Brain Neoplasms/*genetics/*pathology Epithelial-Mesenchymal Transition/*genetics Glioblastoma/*genetics/*pathology Humans Glioblastoma Master transcriptional regulator Mesenchymal transition TAMs Transcriptomic plasticity"],"metadata":{"authorlinks":{}}},"bibtype":"article","biburl":"https://verhaaklab.com/files/verhaak.bib","dataSources":["iFXeF2qjAL2y5TeTz"],"keywords":["brain neoplasms/*genetics/*pathology epithelial-mesenchymal transition/*genetics glioblastoma/*genetics/*pathology humans glioblastoma master transcriptional regulator mesenchymal transition tams transcriptomic plasticity"],"search_terms":["perspective","mesenchymal","transformation","glioblastoma","kim","varn","park","yoon","park","lee","verhaak","paek"],"title":"Perspective of mesenchymal transformation in glioblastoma","year":2021}