A Systems Approach to Brain Tumor Treatment
Brain tumors are among the most lethal tumors. Glioblastoma, the most frequent primary brain tumor in adults, has a median survival time of approximately 15 months after diagnosis or a five-year survival rate of 10%; the recurrence rate is nearly 90%. Unfortunately, this prognosis has not improved f...
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doaj-450566b630024d68bbb09a4beff6d4e32021-07-15T15:31:23ZengMDPI AGCancers2072-66942021-06-01133152315210.3390/cancers13133152A Systems Approach to Brain Tumor TreatmentJames H. Park0Adrian Lopez Garcia de Lomana1Diego M. Marzese2Tiffany Juarez3Abdullah Feroze4Parvinder Hothi5Charles Cobbs6Anoop P. Patel7Santosh Kesari8Sui Huang9Nitin S. Baliga10Institute for Systems Biology, Seattle, WA 98109, USACenter for Systems Biology, University of Iceland, 101 Reykjavik, IcelandBalearic Islands Health Research Institute (IdISBa), 07010 Palma, SpainSt. John’s Cancer Institute, Santa Monica, CA 90401, USADepartment of Neurological Surgery, University of Washington, Seattle, WA 98195, USASwedish Neuroscience Institute, Seattle, WA 98122, USASwedish Neuroscience Institute, Seattle, WA 98122, USADepartment of Neurological Surgery, University of Washington, Seattle, WA 98195, USASt. John’s Cancer Institute, Santa Monica, CA 90401, USAInstitute for Systems Biology, Seattle, WA 98109, USAInstitute for Systems Biology, Seattle, WA 98109, USABrain tumors are among the most lethal tumors. Glioblastoma, the most frequent primary brain tumor in adults, has a median survival time of approximately 15 months after diagnosis or a five-year survival rate of 10%; the recurrence rate is nearly 90%. Unfortunately, this prognosis has not improved for several decades. The lack of progress in the treatment of brain tumors has been attributed to their high rate of primary therapy resistance. Challenges such as pronounced inter-patient variability, intratumoral heterogeneity, and drug delivery across the blood–brain barrier hinder progress. A comprehensive, multiscale understanding of the disease, from the molecular to the whole tumor level, is needed to address the intratumor heterogeneity resulting from the coexistence of a diversity of neoplastic and non-neoplastic cell types in the tumor tissue. By contrast, inter-patient variability must be addressed by subtyping brain tumors to stratify patients and identify the best-matched drug(s) and therapies for a particular patient or cohort of patients. Accomplishing these diverse tasks will require a new framework, one involving a systems perspective in assessing the immense complexity of brain tumors. This would in turn entail a shift in how clinical medicine interfaces with the rapidly advancing high-throughput (HTP) technologies that have enabled the omics-scale profiling of molecular features of brain tumors from the single-cell to the tissue level. However, several gaps must be closed before such a framework can fulfill the promise of precision and personalized medicine for brain tumors. Ultimately, the goal is to integrate seamlessly multiscale systems analyses of patient tumors and clinical medicine. Accomplishing this goal would facilitate the rational design of therapeutic strategies matched to the characteristics of patients and their tumors. Here, we discuss some of the technologies, methodologies, and computational tools that will facilitate the realization of this vision to practice.https://www.mdpi.com/2072-6694/13/13/3152glioblastomabrain metastasesintratumoral heterogeneitysystems biologyprecision medicine |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
James H. Park Adrian Lopez Garcia de Lomana Diego M. Marzese Tiffany Juarez Abdullah Feroze Parvinder Hothi Charles Cobbs Anoop P. Patel Santosh Kesari Sui Huang Nitin S. Baliga |
spellingShingle |
James H. Park Adrian Lopez Garcia de Lomana Diego M. Marzese Tiffany Juarez Abdullah Feroze Parvinder Hothi Charles Cobbs Anoop P. Patel Santosh Kesari Sui Huang Nitin S. Baliga A Systems Approach to Brain Tumor Treatment Cancers glioblastoma brain metastases intratumoral heterogeneity systems biology precision medicine |
author_facet |
James H. Park Adrian Lopez Garcia de Lomana Diego M. Marzese Tiffany Juarez Abdullah Feroze Parvinder Hothi Charles Cobbs Anoop P. Patel Santosh Kesari Sui Huang Nitin S. Baliga |
author_sort |
James H. Park |
title |
A Systems Approach to Brain Tumor Treatment |
title_short |
A Systems Approach to Brain Tumor Treatment |
title_full |
A Systems Approach to Brain Tumor Treatment |
title_fullStr |
A Systems Approach to Brain Tumor Treatment |
title_full_unstemmed |
A Systems Approach to Brain Tumor Treatment |
title_sort |
systems approach to brain tumor treatment |
publisher |
MDPI AG |
series |
Cancers |
issn |
2072-6694 |
publishDate |
2021-06-01 |
description |
Brain tumors are among the most lethal tumors. Glioblastoma, the most frequent primary brain tumor in adults, has a median survival time of approximately 15 months after diagnosis or a five-year survival rate of 10%; the recurrence rate is nearly 90%. Unfortunately, this prognosis has not improved for several decades. The lack of progress in the treatment of brain tumors has been attributed to their high rate of primary therapy resistance. Challenges such as pronounced inter-patient variability, intratumoral heterogeneity, and drug delivery across the blood–brain barrier hinder progress. A comprehensive, multiscale understanding of the disease, from the molecular to the whole tumor level, is needed to address the intratumor heterogeneity resulting from the coexistence of a diversity of neoplastic and non-neoplastic cell types in the tumor tissue. By contrast, inter-patient variability must be addressed by subtyping brain tumors to stratify patients and identify the best-matched drug(s) and therapies for a particular patient or cohort of patients. Accomplishing these diverse tasks will require a new framework, one involving a systems perspective in assessing the immense complexity of brain tumors. This would in turn entail a shift in how clinical medicine interfaces with the rapidly advancing high-throughput (HTP) technologies that have enabled the omics-scale profiling of molecular features of brain tumors from the single-cell to the tissue level. However, several gaps must be closed before such a framework can fulfill the promise of precision and personalized medicine for brain tumors. Ultimately, the goal is to integrate seamlessly multiscale systems analyses of patient tumors and clinical medicine. Accomplishing this goal would facilitate the rational design of therapeutic strategies matched to the characteristics of patients and their tumors. Here, we discuss some of the technologies, methodologies, and computational tools that will facilitate the realization of this vision to practice. |
topic |
glioblastoma brain metastases intratumoral heterogeneity systems biology precision medicine |
url |
https://www.mdpi.com/2072-6694/13/13/3152 |
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