Cyclooxygenase 2-regulated genes an alternative avenue to the development of new therapeutic drugs for colorectal cancer

Colorectal cancer (CRC) is one of the most common and recurrent types of cancer, with high mortality rates. Several clinical trials and meta-analyses have determined that the use of pharmacological inhibitors of cyclooxygenase 2 (COX-2), the enzyme that catalyses the rate-limiting step in the synthe...

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Autores: Hidalgo-Estévez, Alicia M., Stamatakis Andriani, Konstantinos, Jiménez-Martínez, Marta, López-Pérez, Ricardo, Fresno Escudero, Manuel
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/711301
Acceso en línea:http://hdl.handle.net/10486/711301
https://dx.doi.org/10.3389/fphar.2020.00533
Access Level:acceso abierto
Palabra clave:Colon cancer
Cyclooxygenase
Effector genes/proteins
Metastasis
Prostaglandin
Therapy
Tumor development
Biología y Biomedicina / Biología
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spelling Cyclooxygenase 2-regulated genes an alternative avenue to the development of new therapeutic drugs for colorectal cancerHidalgo-Estévez, Alicia M.Stamatakis Andriani, KonstantinosJiménez-Martínez, MartaLópez-Pérez, RicardoFresno Escudero, ManuelColon cancerCyclooxygenaseEffector genes/proteinsMetastasisProstaglandinTherapyTumor developmentBiología y Biomedicina / BiologíaColorectal cancer (CRC) is one of the most common and recurrent types of cancer, with high mortality rates. Several clinical trials and meta-analyses have determined that the use of pharmacological inhibitors of cyclooxygenase 2 (COX-2), the enzyme that catalyses the rate-limiting step in the synthesis of prostaglandins (PG) from arachidonic acid, can reduce the incidence of CRC as well as the risk of recurrence of this disease, when used together with commonly used chemotherapeutic agents. These observations suggest that inhibition of COX-2 may be useful in the treatment of CRC, although the current drugs targeting COX-2 are not widely used since they increase the risk of health complications. To overcome this difficulty, a possibility is to identify genes regulated by COX-2 activity that could give an advantage to the cells to form tumors and/or metastasize. The modulation of those genes as effectors of COX-2 may cancel the beneficial effects of COX-2 in tumor transformation and metastasis. A review of the available databases and literature and our own data have identified some interesting molecules induced by prostaglandins or COX-2 that have been also described to play a role in colon cancer, being thus potential pharmacological targets in colon cancer. Among those mPGES-1, DUSP4, and 10, Programmed cell death 4, Trop2, and many from the TGFβ and p53 pathways have been identified as genes upregulated in response to COX-2 overexpression or PGs in colon carcinoma lines and overexpressed in colon tumor tissue. Here, we review the available evidence of the potential roles of those molecules in colon cancer in the context of PG/COX signaling pathways that could be critical mediators of some of the tumor growth and metastasis advantage induced by COX-2. At the end, this may allow defining new therapeutic targets/drugs against CRC that could act specifically against tumor cells and would be effective in the prevention and treatment of CRC, lacking the unwanted side effects of COX-2 pharmacological inhibitors, providing alternative approaches in colon cancerThis research was funded by grants from“Ministerio de Ciencia e Innovacion” (SAF2013-42850-R and SAF2016-75988-R) “Comunidad de Madrid (S2017/BMD-3671. INFLAMUNE-CM), Fondo de Investigaciones Sanitarias” (BIOIMID) to MF and Institutional grants from“Fundacion Ramon Areces”and“Banco de Santander”. KS was the recipient of a Spanish Association Against Cancer Oncology Investigator grant (AECCAIO).Frontiers Media S.A.Facultad de Ciencias20202020-04-29research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/711301https://dx.doi.org/10.3389/fphar.2020.00533reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/7113012026-06-23T12:46:27Z
dc.title.none.fl_str_mv Cyclooxygenase 2-regulated genes an alternative avenue to the development of new therapeutic drugs for colorectal cancer
title Cyclooxygenase 2-regulated genes an alternative avenue to the development of new therapeutic drugs for colorectal cancer
spellingShingle Cyclooxygenase 2-regulated genes an alternative avenue to the development of new therapeutic drugs for colorectal cancer
Hidalgo-Estévez, Alicia M.
Colon cancer
Cyclooxygenase
Effector genes/proteins
Metastasis
Prostaglandin
Therapy
Tumor development
Biología y Biomedicina / Biología
title_short Cyclooxygenase 2-regulated genes an alternative avenue to the development of new therapeutic drugs for colorectal cancer
title_full Cyclooxygenase 2-regulated genes an alternative avenue to the development of new therapeutic drugs for colorectal cancer
title_fullStr Cyclooxygenase 2-regulated genes an alternative avenue to the development of new therapeutic drugs for colorectal cancer
title_full_unstemmed Cyclooxygenase 2-regulated genes an alternative avenue to the development of new therapeutic drugs for colorectal cancer
title_sort Cyclooxygenase 2-regulated genes an alternative avenue to the development of new therapeutic drugs for colorectal cancer
dc.creator.none.fl_str_mv Hidalgo-Estévez, Alicia M.
Stamatakis Andriani, Konstantinos
Jiménez-Martínez, Marta
López-Pérez, Ricardo
Fresno Escudero, Manuel
author Hidalgo-Estévez, Alicia M.
author_facet Hidalgo-Estévez, Alicia M.
Stamatakis Andriani, Konstantinos
Jiménez-Martínez, Marta
López-Pérez, Ricardo
Fresno Escudero, Manuel
author_role author
author2 Stamatakis Andriani, Konstantinos
Jiménez-Martínez, Marta
López-Pérez, Ricardo
Fresno Escudero, Manuel
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Facultad de Ciencias
dc.subject.none.fl_str_mv Colon cancer
Cyclooxygenase
Effector genes/proteins
Metastasis
Prostaglandin
Therapy
Tumor development
Biología y Biomedicina / Biología
topic Colon cancer
Cyclooxygenase
Effector genes/proteins
Metastasis
Prostaglandin
Therapy
Tumor development
Biología y Biomedicina / Biología
description Colorectal cancer (CRC) is one of the most common and recurrent types of cancer, with high mortality rates. Several clinical trials and meta-analyses have determined that the use of pharmacological inhibitors of cyclooxygenase 2 (COX-2), the enzyme that catalyses the rate-limiting step in the synthesis of prostaglandins (PG) from arachidonic acid, can reduce the incidence of CRC as well as the risk of recurrence of this disease, when used together with commonly used chemotherapeutic agents. These observations suggest that inhibition of COX-2 may be useful in the treatment of CRC, although the current drugs targeting COX-2 are not widely used since they increase the risk of health complications. To overcome this difficulty, a possibility is to identify genes regulated by COX-2 activity that could give an advantage to the cells to form tumors and/or metastasize. The modulation of those genes as effectors of COX-2 may cancel the beneficial effects of COX-2 in tumor transformation and metastasis. A review of the available databases and literature and our own data have identified some interesting molecules induced by prostaglandins or COX-2 that have been also described to play a role in colon cancer, being thus potential pharmacological targets in colon cancer. Among those mPGES-1, DUSP4, and 10, Programmed cell death 4, Trop2, and many from the TGFβ and p53 pathways have been identified as genes upregulated in response to COX-2 overexpression or PGs in colon carcinoma lines and overexpressed in colon tumor tissue. Here, we review the available evidence of the potential roles of those molecules in colon cancer in the context of PG/COX signaling pathways that could be critical mediators of some of the tumor growth and metastasis advantage induced by COX-2. At the end, this may allow defining new therapeutic targets/drugs against CRC that could act specifically against tumor cells and would be effective in the prevention and treatment of CRC, lacking the unwanted side effects of COX-2 pharmacological inhibitors, providing alternative approaches in colon cancer
publishDate 2020
dc.date.none.fl_str_mv 2020
2020-04-29
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/711301
https://dx.doi.org/10.3389/fphar.2020.00533
url http://hdl.handle.net/10486/711301
https://dx.doi.org/10.3389/fphar.2020.00533
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Frontiers Media S.A.
publisher.none.fl_str_mv Frontiers Media S.A.
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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