scholarly journals Phase I/II Trial of Erlotinib and Temozolomide With Radiation Therapy in the Treatment of Newly Diagnosed Glioblastoma Multiforme: North Central Cancer Treatment Group Study N0177

2008 ◽  
Vol 26 (34) ◽  
pp. 5603-5609 ◽  
Author(s):  
Paul D. Brown ◽  
Sunil Krishnan ◽  
Jann N. Sarkaria ◽  
Wenting Wu ◽  
Kurt A. Jaeckle ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Phase I ◽  
Recursive Partitioning ◽  
Growth Factor Receptor ◽  
Treatment Resistance ◽  
Class Iii ◽  
Egfr Amplification ◽  
Phosphatase And Tensin Homolog ◽  
End Point ◽  
Tensin Homolog

Purpose Epidermal growth factor receptor (EGFR) amplification in glioblastoma multiforme (GBM) is a common occurrence and is associated with treatment resistance. Erlotinib, a selective EGFR inhibitor, was combined with temozolomide (TMZ) and radiotherapy (RT) in a phase I/II trial. Patients and Methods Adults not taking enzyme-inducing anticonvulsants after resection or biopsy of GBM were treated with erlotinib (150 mg daily) until progression. Erlotinib was delivered alone for 1 week, then concurrently with TMZ (75 mg mg/m2 daily) and RT (60 Gy), and finally, concurrently with up to six cycles of adjuvant TMZ (200 mg/m2 daily for 5 days every 28 days). The primary end point was survival at 1 year. Results Ninety-seven eligible patients were accrued with a median follow-up time of 22.2 months. By definition, the primary end point was successfully met with a median survival time of 15.3 months. However, there was no sign of benefit in overall survival when comparing N0177 with the RT/TMZ arm of the European Organisation for Research and Treatment of Cancer/National Cancer Institute of Canada trial 26981/22981 (recursive partitioning analysis [RPA] class III, 19 v 21 months; RPA class IV, 16 v 16 months; RPA class V, 8 v 10 months, respectively). Presence of diarrhea, rash, and EGFRvIII, p53, phosphatase and tensin homolog (PTEN), combination EGFR and PTEN, and EGFR amplification status were not predictive (P > .05) of survival. Conclusion Although the primary end point was successfully met using nitrosourea-based (pre-TMZ) chemotherapy era historic controls, there was no sign of benefit compared with TMZ era controls. Analyses of molecular subsets did not reveal cohorts of patients sensitive to erlotinib. TMZ chemotherapy combined with RT resulted in improved outcomes compared with historical controls who received nitrosourea-based chemotherapies.

scholarly journals BRCAness as a Biomarker of Susceptibility to PARP Inhibitors in Glioblastoma Multiforme

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1188
Author(s):  
Mary-Ann Xavier ◽  
Fernando Rezende ◽  
Ricardo Titze-de-Almeida ◽  
Bart Cornelissen
Keyword(s):  
Glioblastoma Multiforme ◽  
Growth Factor Receptor ◽  
Standard Of Care ◽  
Parp Inhibitors ◽  
Genetic Alterations ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog ◽  
Damage Repair ◽  
Cancer Types ◽  
Epidermal Growth

Glioblastoma multiforme (GBM) is the most common primary brain cancer. GBMs commonly acquire resistance to standard-of-care therapies. Among the novel means to sensitize GBM to DNA-damaging therapies, a promising strategy is to combine them with inhibitors of the DNA damage repair (DDR) machinery, such as inhibitors for poly(ADP-ribose) polymerase (PARP). PARP inhibitors (PARPis) have already shown efficacy and have received regulatory approval for breast, ovarian, prostate, and pancreatic cancer treatment. In these cancer types, after PARPi administration, patients carrying specific mutations in the breast cancer 1 (BRCA1) and 2 (BRCA2) suppressor genes have shown better response when compared to wild-type carriers. Mutated BRCA genes are infrequent in GBM tumors, but their cells can carry other genetic alterations that lead to the same phenotype collectively referred to as ‘BRCAness’. The most promising biomarkers of BRCAness in GBM are related to isocitrate dehydrogenases 1 and 2 (IDH1/2), epidermal growth factor receptor (EGFR), phosphatase and tensin homolog (PTEN), MYC proto-oncogene, and estrogen receptors beta (ERβ). BRCAness status identified by accurate biomarkers can ultimately predict responsiveness to PARPi therapy, thereby allowing patient selection for personalized treatment. This review discusses potential biomarkers of BRCAness for a ‘precision medicine’ of GBM patients.

scholarly journals HPAanalyze: an R package that facilitates the retrieval and analysis of the Human Protein Atlas data

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Anh Nhat Tran ◽  
Alex M. Dussaq ◽  
Timothy Kennell ◽  
Christopher D. Willey ◽  
Anita B. Hjelmeland
Keyword(s):  
Growth Factor Receptor ◽  
R Package ◽  
Human Protein ◽  
Web Based ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog ◽  
Automatic Retrieval ◽  
Human Protein Atlas ◽  
Human Proteins ◽  
Data Tables

Abstract Background The Human Protein Atlas (HPA) aims to map human proteins via multiple technologies including imaging, proteomics and transcriptomics. Access of the HPA data is mainly via web-based interface allowing views of individual proteins, which may not be optimal for data analysis of a gene set, or automatic retrieval of original images. Results HPAanalyze is an R package for retrieving and performing exploratory analysis of data from HPA. HPAanalyze provides functionality for importing data tables and xml files from HPA, exporting and visualizing data, as well as downloading all staining images of interest. The package is free, open source, and available via Bioconductor and GitHub. We provide examples of the use of HPAanalyze to investigate proteins altered in the deadly brain tumor glioblastoma. For example, we confirm Epidermal Growth Factor Receptor elevation and Phosphatase and Tensin Homolog loss and suggest the importance of the GTP Cyclohydrolase I/Tetrahydrobiopterin pathway. Additionally, we provide an interactive website for non-programmers to explore and visualize data without the use of R. Conclusions HPAanalyze integrates into the R workflow with the tidyverse framework, and it can be used in combination with Bioconductor packages for easy analysis of HPA data.

scholarly journals Variegated Colors of Pediatric Glioblastoma Multiforme: What to Expect?

Rare Tumors ◽  
2017 ◽  
Vol 9 (2) ◽  
pp. 81-84
Author(s):  
Vivek Immanuel ◽  
Pamela A. Kingsley ◽  
Preety Negi ◽  
Roma Isaacs ◽  
Sarvpreet S. Grewal
Keyword(s):  
Glioblastoma Multiforme ◽  
Pediatric Population ◽  
Malignant Gliomas ◽  
Growth Factor Receptor ◽  
Surgical Excision ◽  
Genetic Alterations ◽  
Adult Brain ◽  
Isocitrate Dehydrogenase 1 ◽  
Term Survival ◽  
Tensin Homolog

Malignant gliomas account for 35-45% of primary brain tumors; among these glioblastoma multiforme (GBM) is the most common adult brain tumor constituting approximately 85%. Its incidence is quite less in the pediatric population and treatment of these patients is particularly challenging. Exposure to ionizing radiation is the only environmental factor found to have any significant association with GBM. Several genetic alterations associated with GBM in adults have been well documented such as epidermal growth factor receptor amplification, overexpression of mouse double minute 2 homolog also known as E3 ubiquitin-protein ligase, Phosphatase and tensin homolog gene mutation, loss of heterozygosity of chromosome 10p and isocitrate dehydrogenase-1 mutation. However, data on genetic mutations in pediatric GBM is still lacking. Exophytic brain stem gliomas are rare tumors and are usually associated with a poor prognosis. The most effective treatment in achieving long-term survival in such patients, is surgical excision of the tumor and then chemoradiotherapy followed by adjuvant chemotherapy by temozolomide. This schedule is the standard treatment for GBM patients. In view of the rarity of pediatric GBM, we report here a case of pontine GBM in a 5-year-old girl.

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