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Refractory Glioblastoma

MedGen UID:
1645398
•Concept ID:
C4687446
•
Neoplastic Process

Definition

A glioblastoma that is resistant to treatment. [from NCI]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVRefractory Glioblastoma

Professional guidelines

PubMed

Lack of Constitutively Active DNA Repair Sensitizes Glioblastomas to Akt Inhibition and Induces Synthetic Lethality with Radiation Treatment in a p53-Dependent Manner.
Palanichamy K, Patel D, Jacob JR, Litzenberg KT, Gordon N, Acus K, Noda SE, Chakravarti A
Mol Cancer Ther 2018 Feb;17(2):336-346. Epub 2017 Aug 24 doi: 10.1158/1535-7163.MCT-17-0429. PMID: 28838997
Twice-daily dosing of temozolomide in combination with fotemustine for the treatment of patients with refractory glioblastoma.
Santoni M, Paccapelo A, Burattini L, Onofri A, Cascinu S
Anticancer Res 2012 Mar;32(3):1099-101. PMID: 22399639

Recent clinical studies

Etiology

Clinical Benefit of Bevacizumab and Irinotecan (BEV+IRI) in Patients With Relapsed/Refractory Glioblastoma (r/rGBM) and its Potential Predictors.
Park JH, Lee HS, Choi JW, Lim SD, Koh HK, Cho KR, Cho J, Koh YC, Yoon SY
Anticancer Res 2022 Dec;42(12):6091-6098. doi: 10.21873/anticanres.16121. PMID: 36456153
Phase I/II study of bevacizumab with BKM120, an oral PI3K inhibitor, in patients with refractory solid tumors (phase I) and relapsed/refractory glioblastoma (phase II).
Hainsworth JD, Becker KP, Mekhail T, Chowdhary SA, Eakle JF, Wright D, Langdon RM, Yost KJ, Padula GDA, West-Osterfield K, Scarberry M, Shaifer CA, Shastry M, Burris HA 3rd, Shih K
J Neurooncol 2019 Sep;144(2):303-311. Epub 2019 Aug 7 doi: 10.1007/s11060-019-03227-7. PMID: 31392595
Role of delayed salvage bevacizumab at symptomatic progression of chemorefractory glioblastoma.
Cuncannon M, Wong M, Jayamanne D, Guo L, Cove N, Wheeler H, Back M
BMC Cancer 2019 May 14;19(1):445. doi: 10.1186/s12885-019-5678-1. PMID: 31088401Free PMC Article
Hypoxia-activated evofosfamide for treatment of recurrent bevacizumab-refractory glioblastoma: a phase I surgical study.
Brenner A, Zuniga R, Sun JD, Floyd J, Hart CP, Kroll S, Fichtel L, Cavazos D, Caflisch L, Gruslova A, Huang S, Liu Y, Lodi A, Tiziani S
Neuro Oncol 2018 Aug 2;20(9):1231-1239. doi: 10.1093/neuonc/noy015. PMID: 29415215Free PMC Article
The Pluripotent Stem-Cell Marker Alkaline Phosphatase is Highly Expressed in Refractory Glioblastoma with DNA Hypomethylation.
Iwadate Y, Suganami A, Tamura Y, Matsutani T, Hirono S, Shinozaki N, Hiwasa T, Takiguchi M, Saeki N
Neurosurgery 2017 Feb 1;80(2):248-256. doi: 10.1093/neuros/nyw026. PMID: 28173571

Diagnosis

Red light-activated depletion of drug-refractory glioblastoma stem cells and chemosensitization of an acquired-resistant mesenchymal phenotype.
Spring BQ, Watanabe K, Ichikawa M, Mallidi S, Matsudaira T, Timerman D, Swain JWR, Mai Z, Wakimoto H, Hasan T
Photochem Photobiol 2025 Jan-Feb;101(1):215-229. Epub 2024 Jun 23 doi: 10.1111/php.13985. PMID: 38922889Free PMC Article
Clinical Benefit of Bevacizumab and Irinotecan (BEV+IRI) in Patients With Relapsed/Refractory Glioblastoma (r/rGBM) and its Potential Predictors.
Park JH, Lee HS, Choi JW, Lim SD, Koh HK, Cho KR, Cho J, Koh YC, Yoon SY
Anticancer Res 2022 Dec;42(12):6091-6098. doi: 10.21873/anticanres.16121. PMID: 36456153
Deep immune profiling reveals targetable mechanisms of immune evasion in immune checkpoint inhibitor-refractory glioblastoma.
Simonds EF, Lu ED, Badillo O, Karimi S, Liu EV, Tamaki W, Rancan C, Downey KM, Stultz J, Sinha M, McHenry LK, Nasholm NM, Chuntova P, Sundström A, Genoud V, Shahani SA, Wang LD, Brown CE, Walker PR, Swartling FJ, Fong L, Okada H, Weiss WA, Hellström M
J Immunother Cancer 2021 Jun;9(6) doi: 10.1136/jitc-2020-002181. PMID: 34083417Free PMC Article
High levels of ubidecarenone (oxidized CoQ(10)) delivered using a drug-lipid conjugate nanodispersion (BPM31510) differentially affect redox status and growth in malignant glioma versus non-tumor cells.
Sun J, Patel CB, Jang T, Merchant M, Chen C, Kazerounian S, Diers AR, Kiebish MA, Vishnudas VK, Gesta S, Sarangarajan R, Narain NR, Nagpal S, Recht L
Sci Rep 2020 Aug 17;10(1):13899. doi: 10.1038/s41598-020-70969-0. PMID: 32807842Free PMC Article
Durable Response to Nivolumab in a Pediatric Patient with Refractory Glioblastoma and Constitutional Biallelic Mismatch Repair Deficiency.
AlHarbi M, Ali Mobark N, AlMubarak L, Aljelaify R, AlSaeed M, Almutairi A, Alqubaishi F, Hussain ME, Balbaid AAO, Said Marie A, AlSubaie L, AlShieban S, alTassan N, Ramkissoon SH, Abedalthagafi M
Oncologist 2018 Dec;23(12):1401-1406. Epub 2018 Aug 13 doi: 10.1634/theoncologist.2018-0163. PMID: 30104292Free PMC Article

Therapy

Piperlongumine conquers temozolomide chemoradiotherapy resistance to achieve immune cure in refractory glioblastoma via boosting oxidative stress-inflamation-CD8(+)-T cell immunity.
Liu F, Zhou Q, Jiang HF, Zhang TT, Miao C, Xu XH, Wu JX, Yin SL, Xu SJ, Peng JY, Gao PP, Cao X, Pan F, He X, Chen XQ
J Exp Clin Cancer Res 2023 May 10;42(1):118. doi: 10.1186/s13046-023-02686-1. PMID: 37161450Free PMC Article
Short-Interval, Low-Dose [ 177 Lu]Lu-Prostate-Specific Membrane Antigen in the Treatment of Refractory Glioblastoma.
More S, Naiker T, Jacobs N, Oompie F, Prasad V
Clin Nucl Med 2023 May 1;48(5):e217-e218. Epub 2023 Mar 5 doi: 10.1097/RLU.0000000000004612. PMID: 36881610
Role of delayed salvage bevacizumab at symptomatic progression of chemorefractory glioblastoma.
Cuncannon M, Wong M, Jayamanne D, Guo L, Cove N, Wheeler H, Back M
BMC Cancer 2019 May 14;19(1):445. doi: 10.1186/s12885-019-5678-1. PMID: 31088401Free PMC Article
Twice-daily dosing of temozolomide in combination with fotemustine for the treatment of patients with refractory glioblastoma.
Santoni M, Paccapelo A, Burattini L, Onofri A, Cascinu S
Anticancer Res 2012 Mar;32(3):1099-101. PMID: 22399639
hIL-13-PE38QQR. NeoPharm.
Barth S
Curr Opin Investig Drugs 2001 Sep;2(9):1309-13. PMID: 11717820

Prognosis

Clinical Benefit of Bevacizumab and Irinotecan (BEV+IRI) in Patients With Relapsed/Refractory Glioblastoma (r/rGBM) and its Potential Predictors.
Park JH, Lee HS, Choi JW, Lim SD, Koh HK, Cho KR, Cho J, Koh YC, Yoon SY
Anticancer Res 2022 Dec;42(12):6091-6098. doi: 10.21873/anticanres.16121. PMID: 36456153
Phase I/II study of bevacizumab with BKM120, an oral PI3K inhibitor, in patients with refractory solid tumors (phase I) and relapsed/refractory glioblastoma (phase II).
Hainsworth JD, Becker KP, Mekhail T, Chowdhary SA, Eakle JF, Wright D, Langdon RM, Yost KJ, Padula GDA, West-Osterfield K, Scarberry M, Shaifer CA, Shastry M, Burris HA 3rd, Shih K
J Neurooncol 2019 Sep;144(2):303-311. Epub 2019 Aug 7 doi: 10.1007/s11060-019-03227-7. PMID: 31392595
Role of delayed salvage bevacizumab at symptomatic progression of chemorefractory glioblastoma.
Cuncannon M, Wong M, Jayamanne D, Guo L, Cove N, Wheeler H, Back M
BMC Cancer 2019 May 14;19(1):445. doi: 10.1186/s12885-019-5678-1. PMID: 31088401Free PMC Article
Durable Response to Nivolumab in a Pediatric Patient with Refractory Glioblastoma and Constitutional Biallelic Mismatch Repair Deficiency.
AlHarbi M, Ali Mobark N, AlMubarak L, Aljelaify R, AlSaeed M, Almutairi A, Alqubaishi F, Hussain ME, Balbaid AAO, Said Marie A, AlSubaie L, AlShieban S, alTassan N, Ramkissoon SH, Abedalthagafi M
Oncologist 2018 Dec;23(12):1401-1406. Epub 2018 Aug 13 doi: 10.1634/theoncologist.2018-0163. PMID: 30104292Free PMC Article
The Pluripotent Stem-Cell Marker Alkaline Phosphatase is Highly Expressed in Refractory Glioblastoma with DNA Hypomethylation.
Iwadate Y, Suganami A, Tamura Y, Matsutani T, Hirono S, Shinozaki N, Hiwasa T, Takiguchi M, Saeki N
Neurosurgery 2017 Feb 1;80(2):248-256. doi: 10.1093/neuros/nyw026. PMID: 28173571

Clinical prediction guides

Clinical Benefit of Bevacizumab and Irinotecan (BEV+IRI) in Patients With Relapsed/Refractory Glioblastoma (r/rGBM) and its Potential Predictors.
Park JH, Lee HS, Choi JW, Lim SD, Koh HK, Cho KR, Cho J, Koh YC, Yoon SY
Anticancer Res 2022 Dec;42(12):6091-6098. doi: 10.21873/anticanres.16121. PMID: 36456153
Phase II trial of ponatinib in patients with bevacizumab-refractory glioblastoma.
Lee EQ, Muzikansky A, Duda DG, Gaffey S, Dietrich J, Nayak L, Chukwueke UN, Beroukhim R, Doherty L, Laub CK, LaFrankie D, Fontana B, Stefanik J, Ruland S, Caruso V, Bruno J, Ligon K, Reardon DA, Wen PY
Cancer Med 2019 Oct;8(13):5988-5994. Epub 2019 Aug 24 doi: 10.1002/cam4.2505. PMID: 31444999Free PMC Article
Durable Response to Nivolumab in a Pediatric Patient with Refractory Glioblastoma and Constitutional Biallelic Mismatch Repair Deficiency.
AlHarbi M, Ali Mobark N, AlMubarak L, Aljelaify R, AlSaeed M, Almutairi A, Alqubaishi F, Hussain ME, Balbaid AAO, Said Marie A, AlSubaie L, AlShieban S, alTassan N, Ramkissoon SH, Abedalthagafi M
Oncologist 2018 Dec;23(12):1401-1406. Epub 2018 Aug 13 doi: 10.1634/theoncologist.2018-0163. PMID: 30104292Free PMC Article
Lack of Constitutively Active DNA Repair Sensitizes Glioblastomas to Akt Inhibition and Induces Synthetic Lethality with Radiation Treatment in a p53-Dependent Manner.
Palanichamy K, Patel D, Jacob JR, Litzenberg KT, Gordon N, Acus K, Noda SE, Chakravarti A
Mol Cancer Ther 2018 Feb;17(2):336-346. Epub 2017 Aug 24 doi: 10.1158/1535-7163.MCT-17-0429. PMID: 28838997
Phase I/II study of oral erlotinib for treatment of relapsed/refractory glioblastoma multiforme and anaplastic astrocytoma.
Kesavabhotla K, Schlaff CD, Shin B, Mubita L, Kaplan R, Tsiouris AJ, Pannullo SC, Christos P, Lavi E, Scheff R, Boockvar JA
J Exp Ther Oncol 2012;10(1):71-81. PMID: 22946346

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