Cargando…

Pathway-Based Drug-Repurposing Schemes in Cancer: The Role of Translational Bioinformatics

Cancer is a set of complex pathologies that has been recognized as a major public health problem worldwide for decades. A myriad of therapeutic strategies is indeed available. However, the wide variability in tumor physiology, response to therapy, added to multi-drug resistance poses enormous challe...

Descripción completa

Detalles Bibliográficos
Autores principales: Hernández-Lemus, Enrique, Martínez-García, Mireya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841291/
https://www.ncbi.nlm.nih.gov/pubmed/33520715
http://dx.doi.org/10.3389/fonc.2020.605680
_version_ 1783643773872373760
author Hernández-Lemus, Enrique
Martínez-García, Mireya
author_facet Hernández-Lemus, Enrique
Martínez-García, Mireya
author_sort Hernández-Lemus, Enrique
collection PubMed
description Cancer is a set of complex pathologies that has been recognized as a major public health problem worldwide for decades. A myriad of therapeutic strategies is indeed available. However, the wide variability in tumor physiology, response to therapy, added to multi-drug resistance poses enormous challenges in clinical oncology. The last years have witnessed a fast-paced development of novel experimental and translational approaches to therapeutics, that supplemented with computational and theoretical advances are opening promising avenues to cope with cancer defiances. At the core of these advances, there is a strong conceptual shift from gene-centric emphasis on driver mutations in specific oncogenes and tumor suppressors—let us call that the silver bullet approach to cancer therapeutics—to a systemic, semi-mechanistic approach based on pathway perturbations and global molecular and physiological regulatory patterns—we will call this the shrapnel approach. The silver bullet approach is still the best one to follow when clonal mutations in driver genes are present in the patient, and when there are targeted therapies to tackle those. Unfortunately, due to the heterogeneous nature of tumors this is not the common case. The wide molecular variability in the mutational level often is reduced to a much smaller set of pathway-based dysfunctions as evidenced by the well-known hallmarks of cancer. In such cases “shrapnel gunshots” may become more effective than “silver bullets”. Here, we will briefly present both approaches and will abound on the discussion on the state of the art of pathway-based therapeutic designs from a translational bioinformatics and computational oncology perspective. Further development of these approaches depends on building collaborative, multidisciplinary teams to resort to the expertise of clinical oncologists, oncological surgeons, and molecular oncologists, but also of cancer cell biologists and pharmacologists, as well as bioinformaticians, computational biologists and data scientists. These teams will be capable of engaging on a cycle of analyzing high-throughput experiments, mining databases, researching on clinical data, validating the findings, and improving clinical outcomes for the benefits of the oncological patients.
format Online
Article
Text
id pubmed-7841291
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-78412912021-01-29 Pathway-Based Drug-Repurposing Schemes in Cancer: The Role of Translational Bioinformatics Hernández-Lemus, Enrique Martínez-García, Mireya Front Oncol Oncology Cancer is a set of complex pathologies that has been recognized as a major public health problem worldwide for decades. A myriad of therapeutic strategies is indeed available. However, the wide variability in tumor physiology, response to therapy, added to multi-drug resistance poses enormous challenges in clinical oncology. The last years have witnessed a fast-paced development of novel experimental and translational approaches to therapeutics, that supplemented with computational and theoretical advances are opening promising avenues to cope with cancer defiances. At the core of these advances, there is a strong conceptual shift from gene-centric emphasis on driver mutations in specific oncogenes and tumor suppressors—let us call that the silver bullet approach to cancer therapeutics—to a systemic, semi-mechanistic approach based on pathway perturbations and global molecular and physiological regulatory patterns—we will call this the shrapnel approach. The silver bullet approach is still the best one to follow when clonal mutations in driver genes are present in the patient, and when there are targeted therapies to tackle those. Unfortunately, due to the heterogeneous nature of tumors this is not the common case. The wide molecular variability in the mutational level often is reduced to a much smaller set of pathway-based dysfunctions as evidenced by the well-known hallmarks of cancer. In such cases “shrapnel gunshots” may become more effective than “silver bullets”. Here, we will briefly present both approaches and will abound on the discussion on the state of the art of pathway-based therapeutic designs from a translational bioinformatics and computational oncology perspective. Further development of these approaches depends on building collaborative, multidisciplinary teams to resort to the expertise of clinical oncologists, oncological surgeons, and molecular oncologists, but also of cancer cell biologists and pharmacologists, as well as bioinformaticians, computational biologists and data scientists. These teams will be capable of engaging on a cycle of analyzing high-throughput experiments, mining databases, researching on clinical data, validating the findings, and improving clinical outcomes for the benefits of the oncological patients. Frontiers Media S.A. 2021-01-14 /pmc/articles/PMC7841291/ /pubmed/33520715 http://dx.doi.org/10.3389/fonc.2020.605680 Text en Copyright © 2021 Hernández-Lemus and Martínez-García http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Hernández-Lemus, Enrique
Martínez-García, Mireya
Pathway-Based Drug-Repurposing Schemes in Cancer: The Role of Translational Bioinformatics
title Pathway-Based Drug-Repurposing Schemes in Cancer: The Role of Translational Bioinformatics
title_full Pathway-Based Drug-Repurposing Schemes in Cancer: The Role of Translational Bioinformatics
title_fullStr Pathway-Based Drug-Repurposing Schemes in Cancer: The Role of Translational Bioinformatics
title_full_unstemmed Pathway-Based Drug-Repurposing Schemes in Cancer: The Role of Translational Bioinformatics
title_short Pathway-Based Drug-Repurposing Schemes in Cancer: The Role of Translational Bioinformatics
title_sort pathway-based drug-repurposing schemes in cancer: the role of translational bioinformatics
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841291/
https://www.ncbi.nlm.nih.gov/pubmed/33520715
http://dx.doi.org/10.3389/fonc.2020.605680
work_keys_str_mv AT hernandezlemusenrique pathwaybaseddrugrepurposingschemesincancertheroleoftranslationalbioinformatics
AT martinezgarciamireya pathwaybaseddrugrepurposingschemesincancertheroleoftranslationalbioinformatics