Discover the Untold Story of Klaus Dieter Michalsky: Life, Legacy, and Achievements

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Introduction

Dr. W.K. Alfred Yung is a distinguished professor of Neuro-Oncology at The University of Texas MD Anderson Cancer Center. His career spans over three decades of dedicated research and clinical work in the field of brain tumors. This article will delve into his education, career highlights, research contributions, and significant achievements that have shaped the landscape of neuro-oncology.

Early Life and Education

Dr. Yung's academic journey began at the University of Minnesota, Minneapolis, where he earned his undergraduate degree. He then pursued his medical degree at the University of Chicago Pritzker School of Medicine. Following his medical degree, he undertook internship and residency training at the University of California, San Diego. His pursuit of specialized knowledge led him to Cornell University School of Medicine and Memorial Sloan-Kettering Cancer Center, where he completed his chief residency and a fellowship.

Career at MD Anderson

In 1981, Dr. Yung joined MD Anderson as an assistant professor and quickly advanced through the faculty ranks. From 1999 to 2015, he served as the co-director of the MDACC Brain Tumor Center, expanding its scope and impact alongside co-director Raymond Sawaya, M.D. He also served as the ad interim chair (1999-2002) and later as chair (2002-2015) of the department of Neuro-Oncology. During his leadership, the department grew to include 24 faculty members and achieved significant milestones, including the development of a National Cancer Institute (NCI)-funded Brain Tumor Clinical Trial Consortium, a Brain Specialized Program of Research Excellence (SPORE), and the D24 smart oncolytic virus program. He held the Margaret and Ben Love Chair of Clinical Cancer Care and dual appointment as professor of Cancer Biology at The University of Texas MD Anderson Cancer Center. He is also a faculty member at the UT Graduate School of Biomedical Sciences in Houston.

Research and Contributions

Dr. Yung's research is focused on developing new therapeutic approaches to block the regulatory mechanisms of brain cancer cells. His primary focus is on development of molecular therapeutic strategies targeting the EGFR and PTEN/PI3 kinase pathways and tumor resistant mechanisms that are crucial to the progression of human glioma. He has published more than 400 peer-reviewed journals.

Some of his significant contributions include:

Discovery of the PTEN gene with Peter Steck.
Leading the study that led to FDA approval of temozolomide for glioblastoma.
Co-leadership of the registration study which led to approval of the drug bevacizumab for recurrent glioblastoma.
Co-chair of the TCGA GBM and LGG committees.
Development and funding of the National Cancer Institute (NCI)-funded Brain Tumor SPORE.
Building of the D24 smart oncolytic virus program.
Leadership in the NCI-funded CNS tumor clinical trial consortia.
Creation of the GBM Agile, a global adaptive clinical trial platform.

Leadership and Recognition

Dr. Yung served as Editor-in-Chief of Neuro-Oncology (2007-2014) and co-chair of the NCI Brain Malignancy Steering Committee (2011-2017). He was also appointed to Vice President Biden’s Cancer Moonshot Blue Ribbon Panel in 2016.

Selected Publications

Dr. Yung's extensive research has resulted in numerous publications in peer-reviewed journals. Some of his recent publications include:

Wu S, Li X, Gao F, de Groot JF, Koul D, Yung WKA. PARP-mediated PARylation of MGMT is critical to promote repair of temozolomide-induced O6-methylguanine DNA damage in glioblastoma. Neuro-Oncology, 2021.
Weathers SP, Rood-Breithaupt J, de Groot J, Thomas G, Manfrini M, Penas-Prado M, Puduvalli VK, Zwingelstein C, Yung WKA. Results of a phase I trial to assess the safety of macitentan in combination with temozolomide for the treatment of recurrent glioblastoma. Neurooncol Adv 3(1):vdab141, 2021.
Wu S, Gao F, Zheng S, Zhang C, Martinez-Ledesma E, Ezhilarasan R, Ding J, Li X, Feng N, Multani A, Sulman EP, Verhaak RG, de Groot JF, Heffernan TP, Yung WKA, Koul D.. EGFR Amplification Induces Increased DNA Damage Response and Renders Selective Sensitivity to Talazoparib (PARP Inhibitor) in Glioblastoma. Clinical Cancer Research 26(6):1395-1407, 2020.
Puduvalli VK, Wu J, Yuan Y, Armstrong TS, Vera E, Wu J, Xu J, Giglio P, Colman H, Walbert T, Raizer J, Groves MD, Tran D, Iwamoto F, Avgeropoulos N, Paleologos N, Fink K, Peereboom D, Chamberlain M, Merrell R, Penas Prado M, Yung WKA, Gilbert MR.. A Bayesian Adaptive Randomized Phase II Multicenter Trial of Bevacizumab with or without Vorinostat in Adults with Recurrent Glioblastoma. Neuro-Oncology 062, 2020.
van den Bent M, Azaro A, De Vos F, Sepulveda J, Yung WKA, Wen PY, Lassman AB, Joerger M, Tabatabai G, Rodon J, Tiedt R, Zhao S, Kirsilae T, Cheng Y, Vicente S, Balbin OA, Zhang H, Wick W.. A Phase Ib/II, open-label, multicenter study of INC280 (capmatinib) alone and in combination with buparlisib (BKM120) in adult patients with recurrent glioblastoma. Journal of Neuro-Oncology 146(1):79-89, 2020.
GLASS Consortium. Longitudinal molecular trajectories of diffuse glioma in adults. Nature 576(7785):112-120, 2019.
de Groot J, Penas-Prado M, Alfaro-Munoz KD, Hunter K, Pei B, O'Brien BJ, Weathers SP, Loghin M, Kamiya Matsouka C, Yung WKA, Mandel J, Wu J, Yuan Y, Zhou S, Fuller GN, Huse J, Rao G, Weinberg JS, Prabhu SS, McCutcheon IE, Lang FF, Ferguson SD, Sawaya R, Colen R, Yadav SS, Blando J, Vence L, Allison J, Sharma P, Heimberger AB.. Window-of-opportunity clinical trial of pembrolizumab in patients with recurrent glioblastoma reveals predominance of immune-suppressive macrophages. Neuro-Oncology 185, 2019.
Ding J, Wu S, Zhang C, Garyali A, Martinez-Ledesma E, Gao F, Pokkulandra A, Li X, Bristow C, Carugo A, Koul D, Yung WA.. BRCA1 identified as a modulator of temozolomide resistance in P53 wild-type GBM using a high-throughput shRNA-based synthetic lethality screening. American Journal of Cancer Research 9(11):2428-2441, 2019.
Li X, Martinez-Ledesma E, Zhang C, Gao F, Zheng S, Ding J, Wu S, Nguyen N, Clifford SC, Wen PY, Ligon KL, Yung WKA, Koul D.. Tie2-FGFR1 Interaction Induces Adaptive PI3K Inhibitor Resistance by Upregulating Aurora A/PLK1/CDK1 Signaling in Glioblastoma. Cancer Research 79(19):5088-5101, 2019.
Zheng S, Alfaro-Munoz K, Wei W, Wang X, Wang F, Eterovic AK, Shaw KRM, Meric-Bernstam F, Fuller GN, Chen K, Verhaak RG, Mills GB, Yung WKA, Weathers SP, de Groot JF.. Prospective Clinical Sequencing of Adult Glioma. Molecular Cancer Therapeutics(18(5)):991-1000, 2019.
Harrison RA, Anderson MD, Cachia D, Kamiya-Matsuoka C, Weathers SS, O'Brien BJ, Penas-Prado M, Yung WKA, Wu J, Yuan Y, de Groot JF.. Clinical trial participation of patients with glioblastoma at The University of Texas MD Anderson Cancer Center. European Journal of Cancer 112:83-93, 2019.
Wen PY, Touat M, Alexander BM, Mellinghoff IK, Ramkissoon S, McCluskey CS, Pelton K, Haidar S, Basu SS, Gaffey SC, Brown LE, Martinez-Ledesma JE, Wu S, Kim J, Wei W, Park MA, Huse JT, Kuhn JG, Rinne ML, Colman H, Agar NYR, Omuro AM, DeAngelis LM, Gilbert MR, de Groot JF, Cloughesy TF, Chi AS, Roberts TM, ZhaoJJ, Lee EQ, Nayak L, Heath JR, Horky LL, Batchelor TT, Beroukhim R, Chang SM, Ligon AH, Dunn IF, Koul D, Young GS, Prados MD, Reardon DA, Yung WKA, Ligon KL.. Buparlisib in Patients With Recurrent Glioblastoma Harboring Phosphatidylinositol 3-Kinase Pathway Activation: An Open-Label, Multicenter, Multi-Arm, Phase II Trial. Journal of Clinical Oncology 37(9):741-750, 2019.
Lang FF, Conrad C, Gomez-Manzano C, Yung WKA, Sawaya R, Weinberg JS, Prabhu SS, Rao G, Fuller GN, Aldape KD, Gumin J, Vence LM, Wistuba I, Rodriguez-Canales J, Villalobos PA, Dirven CMF, Tejada S, Valle RD, Alonso MM, Ewald B, Peterkin JJ, Tufaro F, Fueyo J.. Phase I Study of DNX-2401 (Delta-24-RGD) Oncolytic Adenovirus: Replication and Immunotherapeutic Effects in Recurrent Malignant Glioma. J Clin Oncol 36(14):1419-1427, 2018.
Ali AN, Zhang P, Yung WKA, Chen Y, Movsas B, Urtasun RC, Jones CU, Choi KN, Michalski JM, Fischbach AJ, Markoe AM, Schultz CJ, Penas-Prado M, Garg MK, Hartford AC, Kim HE, Won M, Curran WJ Jr.. NRG oncology RTOG 9006: a phase III randomized trial of hyperfractionated radiotherapy (RT) and BCNU versus standard RT and BCNU for malignant glioma patients. Journal of Neuro-Oncology 137(1):39-47, 2018.
Alexander BM, Ba S, Berger MS, Berry DA, Cavenee WK, Chang SM, Cloughesy TF, Jiang T, Khasraw M, Li W, Mittman R, Poste GH, Wen PY, Yung WKA, Barker AD.. GBM AGILE Network. Adaptive Global Innovative Learning Environment for Glioblastoma: GBM AGILE. Clinical Cancer Research 24(4):737-743, 2018.
Wu S, Wang S, Gao F, Li L, Zheng S, Yung WKA, Koul D.. Activation of WEE1 confers resistance to PI3K inhibition in glioblastoma. Neuro Oncology 20(1):78-91, 2018.
Nghiemphu PL, Ebiana VA, Wen P, Gilbert M, Abrey LE, Lieberman F, DeAngelis LM, Robins HI, Yung WKA, Chang S, Drappatz J, Mehta MP, Levin VA, Aldape K, Dancey JE, Wright JJ, Prados M, Kuhn J, Cloughesy TF.. Phase I study of sorafenib and tipifarnib for recurrent glioblastoma: NABTC 05-02. Journal of Neuro-Oncology 136(1):79-86, 2018.
Ong DST, Hu B, Ho YW, Sauvé CG, Bristow CA, Wang Q, Multani AS, Chen P, Nezi L, Jiang S, Gorman CE, Monasterio MM, Koul D, Marchesini M, Colla S, Jin EJ, Sulman EP, Spring DJ, Yung WA, Verhaak RGW, Chin L, Wang YA, DePinho RA.. PAF promotes stemness and radioresistance of glioma stem cells. Proc Natl Acad Sci USA 114(43):E9086-E9095, 2017.
Alexander BM, Ba S, Berger MS, Berry DA, Cavenee WK, Chang SM, Cloughesy TF, Jiang T, Khasraw M, Li W, Mittman R, Poste GH, Wen PY, Yung WKA, Barker AD;. Adaptive Global Innovative Learning Environment for Glioblastoma:. GBM AGILE Network. e-Pub 2017.
Wang Y, Wu S, Zheng S, Wang S, Wali A, Ezhilarasan R, Sulman EP, Koul D, Alfred Yung WK.. APOBEC3G acts as a therapeutic target in mesenchymal gliomas by sensitizing cells to radiation-induced cell death. Oncotarget 8(33):54285-54296, 2017.
Koul D, Wang S, Wu S, Saito N, Zheng S, Gao F, Kaul I, Setoguchi M, Nakayama K, Koyama K, Shiose Y, Sulman EP, Hirota Y, Yung WKA.. Preclinical therapeutic efficacy of a novel blood-brain barrier-penetrant dual PI3K/mTOR inhibitor with preferential response in PI3K/PTEN mutant glioma. Oncotarget. e-Pub 2017.
Weathers SP, Han X, Liu DD, Conrad CA, Gilbert MR, Loghin ME, O'Brien BJ, Penas-Prado M, Puduvalli VK, Tremont-Lukats I, Colen RR, Yung WKA, de Groot JF.. A randomized phase II trial of standard dose bevacizumab versus low dose bevacizumab plus lomustine (CCNU) in adults with recurrent glioblastoma. Neurooncol, 2016.
Wu S, Wang S, Zheng S, Verhaak R, Koul D, Yung WK.. MSK1-Mediated β-Catenin Phosphorylation Confers Resistance to PI3K/mTOR Inhibitors in Glioblastoma. Mol Cancer Ther, 2016.
Cortes-Santiago N, Hossain MB, Gabrusiewicz K, Fan X, Gumin J, Marini FC, Alonso MM, Lang F, Yung WK, Fueyo J, Gomez-Manzano C.. Soluble Tie2 overrides the heightened invasion induced by anti-angiogenesis therapies in gliomas. Oncotarget, 2016.
Hodges TR, Ferguson SD, Caruso HG, Kohanbash G, Zhou S, Cloughesy TF, Berger MS, Poste GH, Khasraw M, Ba S, Jiang T, Mikkelson T, Yung WK, de Groot JF, Fine H, Cantley LC, Mellinghoff IK, Mitchell DA, Okada H, Heimberger AB. Prioritization schema for immunotherapy clinical trials in glioblastoma. Oncoimmunology. e-Pub 2016.
Wu S, Wang S, Zheng S, Verhaak R, Koul D, Yung WK.. MSK1-Mediated beta-Catenin Phosphorylation Confers Resistance to PI3K/mTOR Inhibitors in Glioblastoma. Mol Cancer Ther(15 (7)):1656-1668, 2016.
Ceccarelli M, Barthel FP, Malta TM, Sabedot TS, Salama SR, Murray BA, Morozova O, Newton Y, Radenbaugh A, Pagnotta SM, Anjum S, Wang J, Manyam G, Zoppoli P, Ling S, Rao AA, Grifford M, Cherniack AD, Zhang H, Poisson L, Carlotti CG Jr, Tirapelli DP, Rao A, Mikkelsen T, Lau CC, Yung WK, Rabadan R, Huse J, Brat DJ, Lehman NL, Barnholtz-Sloan JS, Zheng S, Hess K, Rao G, Meyerson M, Beroukhim R, Cooper L, Akbani R, Wrensch M, Haussler D, Aldape KD, Laird PW, Gutmann DH; TCGA Research Network, Noushmehr H, Iavarone A, Verhaak RG.. Molecular Profiling Reveals Biologically Discrete Subsets and Pathways of Progression in Diffuse Glioma. Cell. e-Pub 2016.
Raizer JJ, Giglio P, Hu J, Groves M, Merrell R, Conrad C, Phuphanich S, Puduvalli VK, Loghin M, Paleologos N, Yuan Y, Liu D, Rademaker A, Yung WK, Vaillant B, Rudnick J, Chamberlain M, Vick N, Grimm S, Tremont-Lukats IW, De Groot J, Aldape K, Gilbert MR;. Brain Tumor Trials Collaborative. A phase II study of bevacizumab and erlotinib after radiation and temozolomide in MGMT unmethylated GBM patients. J Neurooncol, 2016.
Liu Q, Liu Y, Li W, Wang X, Sawaya R, Lang FF, Yung WK, Chen K, Fuller GN, Zhang W. Genetic, epigenetic, and molecular landscapes of multifocal and multicentric glioblastoma. Acta Neuropathol 130(4):587-97, 2015.
Kim SJ, Lee HJ, Kim MS, Choi HJ, He J, Wu Q, Aldape K, Weinberg JS, Yung WK, Conrad CA, Langley RR, Lehembre F, Regenass U, Fidler IJ. Macitentan, a Dual Endothelin Receptor Antagonist, in Combination with Temozolomide Leads to Glioblastoma Regression and Long-term Survival in Mice. Clin Cancer Res 21(20):4630-41, 2015.
Ellingson BM, Bendszus M, Boxerman J, Barboriak D, Erickson BJ, Smits M, Nelson SJ, Gerstner E, Alexander B, Goldmacher G, Wick W, Vogelbaum M, Weller M, Galanis E, Kalpathy-Cramer J, Shankar L, Jacobs P, Pope WB, Yang D, Chung C, Knopp MV, Cha S, van den Bent MJ, Chang S, Yung WK, Cloughesy TF, Wen PY, Gilbert MR, Jumpstarting Brain Tumor Drug Development Coalition Imaging Standardization Steering Committee. Jumpstarting Brain Tumor Drug Development Coalition Imaging Standardization Steering Committee. Consensus recommendations for a standardized Brain Tumor Imaging Protocol in clinical trials. Neuro Oncol 17(9):1188-98, 2015.
Cancer Genome Atlas Research Network, Brat DJ, Verhaak RG, Aldape KD, Yung WK, Salama SR, Cooper LA, Rheinbay E, Miller CR, Vitucci M, Morozova O, Robertson AG, Noushmehr H, Laird PW, Cherniack AD, Akbani R, Huse JT, Ciriello G, Poisson LM, Barnholtz-Sloan JS, Berger MS, Brennan C, Colen RR, Colman H, Flanders AE, Giannini C, Grifford M, Iavarone A, Jain R, Joseph I, Kim J, Kasaian K, Mikkelsen T, Murray BA, O'Neill BP, Pachter L, Parsons DW, Sougnez C, Sulman EP, Vandenberg SR, Van Meir EG, von Deimling A, Zhang H, Crain D, Lau K, Mallery D, Morris S, Paulauskis J, Penny R, Shelton T, Sherman M, Yena P, Black A, Bowen J, Dicostanzo K, Gastier-Foster J, Leraas KM, Lichtenberg TM, Pierson CR, Ramirez NC, Taylor C, Weaver S, Wise L, Zmuda E, Davidsen T, Demchok JA, Eley G, Ferguson ML, Hutter CM, Mills Shaw KR, Ozenberger BA, Sheth M, Sofia HJ, Tarnuzzer R, Wang Z, Yang L, Zenklusen JC, Ayala B, Baboud J, Chudamani S, Jensen MA, Liu J, Pihl T, Raman R, Wan Y, Wu Y, Ally A, Auman JT, Balasundaram M, Balu S, Baylin SB, Beroukhim R, Bootwalla MS, Bowlby R, Bristow CA, Brooks D, Butterfield Y, Carlsen R, Carter S, Chin L, Chu A, Chuah …

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