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Nature Medicine volume 29, pages 2402–2405 (2023 )Cite this article Display Images In Real Time
A breakthrough in drug discovery for glioblastoma requires serial collection of tissue from the central nervous system via window of opportunity trials
Therapeutic drug development in glioblastoma has remained static despite numerous clinical trials, advances in tumor biology, and substantial public interest. Since 2005, more than 1,250 interventional glioblastoma trials have been registered on ClinicalTrials.gov. Of these, 1,100 are phase 1 or 2 trials, most of which are dose-escalation studies. Unfortunately, these often provide little insight into whether drugs reach the tumor, exert a biological effect, or can overcome mechanisms of resistance. Trials often evaluate drugs that show promise in early development but subsequently fail at later stages1. Biological understanding of these failures requires tissue samples before and after treatment, but the collection of these has not been a routine element of either neurosurgical practice or drug development in neuro-oncology. Window of opportunity (WoO) trials can help to determine the mechanisms of drug failure, but expanding their use requires a clearly defined nomenclature, serial access to tissue, and standardized design principles and outcomes. To achieve the clinical success seen for other malignancies, a culture change within the neurosurgical and neuro-oncology community is necessary to support repeated tissue collection from the central nervous system (CNS).
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We thank C. Haynes, M. Bell-Johnston, S. Pressley and the other SNO staff for their administrative and logistical support; and M. Espey, S. Forry, L. Hubbard and A. Tawab-Amiri for their input and review of the manuscript. This article represents the opinion of the authors. It does not represent the opinion or policy of the National Institutes of Health of the US Federal Government.
The Preston Robert Tisch Brain Tumor Center at Duke, Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA
Kirit Singh, Kelly M. Hotchkiss, Annick Desjardins, David M. Ashley, Anoop P. Patel & Mustafa Khasraw
Mayo Clinic, Rochester, MN, USA
Ian F. Parney & Evanthia Galanis
Division of Neuro-Oncology, Department of Neurological Surgery, University of California San Francisco (UCSF), San Francisco, CA, USA
National Institute of Health, Bethesda, MD, USA
Ivy Brain Tumor Center, The Barrow Neurological Institute, Phoenix, AZ, USA
Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany
German Cancer Research Center (DKFZ), Heidelberg, Germany
Michael Platten & Wolfgang Wick
Department of Neurosurgery, Stanford University, School of Medicine, Stanford, CA, USA
Center for Neuro-Oncology, Dana Farber Cancer Institute and Harvard Medical School, Boston, MA, USA
Department of Radiological Sciences, Oncology and Anatomical Pathology, Sapienza University of Rome, Rome, Italy
Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA
Neuro-Oncology Program, University of California Los Angeles (UCLA), Los Angeles, CA, USA
Miami Cancer Institute, Miami, FL, USA
Erasmus MC Cancer Institute, Rotterdam, The Netherlands
Massachusetts General Hospital, Boston, MA, USA
National Brain Tumor Society (NBTS), Newton, MA, USA
Kirk Tanner & David Aarons
School of Medicine, University of Leeds, Leeds, UK
US Food and Drug Administration, Silver Spring, MD, USA
Department of Neurooncology, Heidelberg University, Heidelberg, Germany
Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
School of Medicine, Yale University, New Haven, CT, USA
School of Cancer Sciences, University of Glasgow, Glasgow, UK
Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK
Surgical Neuro-Oncology, Department of Neurology, Duke University Medical Center, Durham, NC, USA
Brigham and Women’s Hospital, Boston, MA, US
Department of Neurology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
Department of NeuroOncology, H. Lee Moffit Cancer Center and Research Institute, Tampa, FL, USA
Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria
Department of Neurological Surgery, UCSF Brain Tumor Center, San Francisco, CA, USA
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M. Platten reports consultant or advisory roles for non-financial support from Roche; personal fees and non-financial support from Bayer; personal fees from Novartis and Apogenix; non-financial support from Pfizer; personal fees from Affiris outside the submitted work; a patent EP2753315B1 licensed to Bayer; a patent EP2800580B1 issued; a patent US20180155403A1 pending; a patent US20180246118A1 pending; a patent US20170254803A1 pending; a patent WO2018146010A1 licensed to Bayer; a patent WO2019101643A1 licensed to Bayer; a patent WO2019101647A1 licensed to Bayer; a patent WO2019101641A1 licensed to Bayer; and a patent WO2019101642A1 licensed to Bayer. E.G. has received honoraria for advisory board participation from Kiyatec, Inc. (personal compensation), Karyopharm Therapeutics, Inc. for Data Safety and Monitoring Board participation (compensation to employer), and Boston Scientific for Data Monitoring Committee (compensation to employer); institutional grant funding from Servier Pharmaceuticals LLC (formerly Agios Pharmaceuticals, Inc.), Celgene, MedImmune, Inc. and Denovo Biopharma. M.L. reports consultant or advisory roles for Tocagen, SQZ Technologies, VBI, InCephalo Therapeutics and Pyramid Bio; reports non-research consulting roles for Stryker; reports research support from Arbor, Bristol-Myers Squibb, Accuray, DNAtrix, Tocagen, Biohaven and Kyrin-Kyowa; and has patents for focused radiation plus checkpoint inhibitors and local chemotherapy plus checkpoint inhibitors. P.Y.W. reports consultant or advisory roles for Astra Zeneca, Black Diamond, Celularity, Chimerix, Day One Bio, Genenta, Glaxo Smith Kline, Merck, Mundipharma, Novartis, Novocure, Nuvation Bio, Prelude Therapeutics, Sapience, Servier, Sagimet, Vascular Biogenics and VBI Vaccines; reports research support from Astra Zeneca, Black Diamond, Celularity, Chimerix, Day One Bio, Genenta, Glaxo Smith Kline, Merck, Mundipharma, Novartis, Novocure, Nuvation Bio, Prelude Therapeutics, Sapience, Servier, Sagimet, Vascular Biogenics and VBI Vaccines; and is an editor for UpToDate and Elsevier. H.C. reports advisory board or consultant roles for Best Doctors/Teladoc, Orbus Therapeutics, Bristol Meyers Squibb, Regeneron, Novocure and PPD/Chimerix; and reports research funding from (site PI/institutional contract): Orbus, GCAR, Array BioPharma, Karyopharm Therapeutics, Nuvation Bio, Bayer, Bristol Meyer Squib, Sumitomo Dainippon Pharma Oncology, Samus Therapeutics and Erasca. T.F.C. is cofounder, major stock holder, consultant and board member of Katmai Pharmaceuticals; holds stock for Erasca; is a member of the board and paid consultant for the 501c3 Global Coalition for Adaptive Research; holds stock in Chimerix and receives milestone payments and possible future royalties; is a member of the scientific advisory board for Break Through Cancer and Cure Brain Cancer Foundation; has provided paid consulting services to BlueRock, Vida Ventures, Lista Therapeutics, Stemline, Novartis, Roche, Sonalasense, Sagimet, Clinical Care Options, Ideology Health, Servier, Jubilant, Immvira, Gan & Lee, BrainStorm, Katmai, Sapience, Inovio, Vigeo Therapeutics, DNATrix, Tyme, SDP, Kintara, Bayer, Merck, Boehinger Ingelheim, VBL, Amgen, Kiyatec, Odonate Therapeutics QED, Medefield, Pascal Biosciences, Bayer, Tocagen, Karyopharm, GW Pharma, Abbvie, VBI, Deciphera, VBL, Agios, Genocea, Celgene, Puma, Lilly, BMS, Cortice, Novocure, Novogen, Boston Biomedical, Sunovion, Insys, Pfizer, Notable labs, Medqia, Trizel and Medscape; and has contracts with UCLA for the Brain Tumor Program with Roche, VBI, Merck, Novartis, BMS, AstraZeneca, Servier and AstraZeneca. The Regents of the University of California (T.F.C. employer) has licensed intellectual property co-invented by T.F.C. to Katmai Pharmaceuticals. M.P.M. reports consultancy roles for Kazia, Novocure, Zap, Xoft, Karyopharm and Sapience; advisory roles with Mevion Technological Advisory Board; is on the board of directors for Xcision (unremunerated) and Oncoceutics; and is a stockholder in Chimerix. I.A.R. reports consultant or advisory roles for Boehringer Ingelheim and Forma Therapeutics; and research funding from Astex Pharmaceuticals and GSK. A.D. reports consultant roles for Orbus Therapeutics and Midatech Ltd; research funding paid to the institution from Orbus Therapeutics and Midatech Ltd; stock options for Istari Oncology; and patents for the treatment of cancer with the oncolytic poliovirus. K.T. reports consultant roles for Oncohereos Biosciences, Cordance Medical, Inovio Pharmaceuticals, Novartis and Day One Biopharmaceuticals and share and board participation in Sage Therapeutics, Oncology and Telo Therapeutics. S. Short reports personal fees for lecturing from Bayer and consulting or advisory board roles for Abbvie, Blue Earth Therapeutics, HOX therapeutics and Tocagen; and research grant support from Apollomics. W.W. reports consultancy roles and/or non-financial support from Apogenix, Astra Zeneca, Bayer, MSD, Pfizer, Novartis and Roche with compensation paid to the institution. S.J.B. has received research grants from Kite, Incyte, Eli Lilly, GSK and Novocure; and honoraria for advisory board participation or consulting from Kiyatec, Novocure, Bayer and Sumitomo Dainippon. D.M.A. reports stock and other ownership interests in Diverse Biotech and Jackson Laboratory for Genomic Medicine; and patents, royalties or other intellectual property for ‘Methods for predicting tumor response to immunotherapy, US provisional application no. 62/787’ and ‘Methods for predicting tumor response to immunotherapy, US provisional application no. 62/620,577’. A.J.C. reports research funding and honoraria from AstraZeneca. A.P.P. reports a consultant role for Syapse and a consultant and equity ownership role in Sygnomics. M.W. has received research grants from Quercis and Versameb, and honoraria for lectures or advisory board participation or consulting from Bayer, Curevac, Medac, Novartis, Novocure, Orbus, Philogen, Roche and Sandoz. M.A.V. reports honoraria or consulting roles with Chimerix and Midatech Pharma; grants and contracts to the H Lee Moffitt Cancer Center and Research Institute from DeNovo, Chimerix, Oncosynergy and Infuseon (Cleveland Clinic), as well as patents relating to Infuseon (Cleveland Clinic). M. Preusser has received honoraria for lectures, consultation or advisory board participation from Bayer, Bristol-Myers Squibb, Novartis, Gerson Lehrman Group, CMC Contrast, GlaxoSmithKline, Mundipharma, Roche, BMJ Journals, MedMedia, Astra Zeneca, AbbVie, Lilly, Medahead, Daiichi Sankyo, Sanofi, Merck Sharp & Dome, Tocagen, Adastra, Gan & Lee Pharmaceuticals and Servier. M.K. reports consultant or advisory roles for Manarini, Janssen, AbbVie, Ipsen, Novocure, Roche and Jackson Laboratory for Genomic Medicine; research funding from Personalis, Daiichi Sankyo, Immorna Therrapeutics, AbbVie, Bristol-Myers Squibb and Specialised Therapeutics. All other authors report no competing interests.
Singh, K., Hotchkiss, K.M., Parney, I.F. et al. Correcting the drug development paradigm for glioblastoma requires serial tissue sampling. Nat Med 29, 2402–2405 (2023). https://doi.org/10.1038/s41591-023-02464-8
DOI: https://doi.org/10.1038/s41591-023-02464-8
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