CTLA-4 blockade in the treatment of colorectal cancer with microsatellite instability

Context: Colorectal cancer is one of the most common tumours worldwide, with around 10-15% of these related to microsatellite instability which is, in turn, responsible for a high neoantigen load and subsequent high tumour mutational burden. These characteristics are responsible for the poor respons...

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Autores principales:	Diana Russo, Francisco Mendes
Formato:	article
Lenguaje:	EN
Publicado:	Shiraz University of Medical Sciences 2021
Materias:	colorectal cancer ctla-4 immune checkpoint immunotherapy ipilimumab microsatellite instability Medicine R
Acceso en línea:	https://doaj.org/article/cf9dbae49f62401a8b71557d294ccb74
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spelling	oai:doaj.org-article:cf9dbae49f62401a8b71557d294ccb742021-11-14T06:50:29ZCTLA-4 blockade in the treatment of colorectal cancer with microsatellite instability2783-243010.30476/acrr.2021.90603.1093https://doaj.org/article/cf9dbae49f62401a8b71557d294ccb742021-03-01T00:00:00Zhttps://colorectalresearch.sums.ac.ir/article_47431_ac63d1a4093a549920d81669e44aa075.pdfhttps://doaj.org/toc/2783-2430Context: Colorectal cancer is one of the most common tumours worldwide, with around 10-15% of these related to microsatellite instability which is, in turn, responsible for a high neoantigen load and subsequent high tumour mutational burden. These characteristics are responsible for the poor response of these tumours to chemotherapy, highlighting the need for a different approach in the treatment of patients with microsatellite unstable colorectal cancer. Immunotherapy was proven important in the treatment of these patients, with immune checkpoint inhibition such as CTLA-4 blockade being one of the most promising targets so far. Evidence Acquisition: A PubMed search was done on February 2021 where the used query obtained a total of 33 articles. After the inclusion and exclusion criteria, a total of 21 articles were obtained and used in this narrative review. Results: Several studies with microsatellite unstable colorectal tumours have been done in order to evaluate the advantages and adverse events of CTLA-4 blockade in these patients. Studies show a benefit regarding the progression-free survival, overall survival and overall response rates in patients receiving ipilimumab (anti-CTLA-4) when compared to those who weren’t. Besides, the main adverse events are manageable and are more tolerable than those observed with chemotherapy. Nonetheless, unlike PD-1 blockade, anti-CTLA-4 drugs are currently only approved for the use as a combination therapy in microsatellite unstable colorectal cancer, still awaiting approval as a monotherapy. Conclusion: Microsatellite unstable colorectal tumours deserve a different treatment path, as their characteristics make these tumours poor responders to chemotherapy while at the same time great candidates for immunotherapy, namely with CTLA-4 inhibitors. KEY-WORDS Colorectal cancer; CTLA-4; Immune checkpoint; Immunotherapy; Ipilimumab; Microsatellite instabilityDiana RussoFrancisco MendesShiraz University of Medical Sciencesarticlecolorectal cancerctla-4immune checkpointimmunotherapyipilimumabmicrosatellite instabilityMedicineRENIranian Journal of Colorectal Research, Vol 9, Iss 1, Pp 1-6 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	colorectal cancer ctla-4 immune checkpoint immunotherapy ipilimumab microsatellite instability Medicine R
spellingShingle	colorectal cancer ctla-4 immune checkpoint immunotherapy ipilimumab microsatellite instability Medicine R Diana Russo Francisco Mendes CTLA-4 blockade in the treatment of colorectal cancer with microsatellite instability
description	Context: Colorectal cancer is one of the most common tumours worldwide, with around 10-15% of these related to microsatellite instability which is, in turn, responsible for a high neoantigen load and subsequent high tumour mutational burden. These characteristics are responsible for the poor response of these tumours to chemotherapy, highlighting the need for a different approach in the treatment of patients with microsatellite unstable colorectal cancer. Immunotherapy was proven important in the treatment of these patients, with immune checkpoint inhibition such as CTLA-4 blockade being one of the most promising targets so far. Evidence Acquisition: A PubMed search was done on February 2021 where the used query obtained a total of 33 articles. After the inclusion and exclusion criteria, a total of 21 articles were obtained and used in this narrative review. Results: Several studies with microsatellite unstable colorectal tumours have been done in order to evaluate the advantages and adverse events of CTLA-4 blockade in these patients. Studies show a benefit regarding the progression-free survival, overall survival and overall response rates in patients receiving ipilimumab (anti-CTLA-4) when compared to those who weren’t. Besides, the main adverse events are manageable and are more tolerable than those observed with chemotherapy. Nonetheless, unlike PD-1 blockade, anti-CTLA-4 drugs are currently only approved for the use as a combination therapy in microsatellite unstable colorectal cancer, still awaiting approval as a monotherapy. Conclusion: Microsatellite unstable colorectal tumours deserve a different treatment path, as their characteristics make these tumours poor responders to chemotherapy while at the same time great candidates for immunotherapy, namely with CTLA-4 inhibitors. KEY-WORDS Colorectal cancer; CTLA-4; Immune checkpoint; Immunotherapy; Ipilimumab; Microsatellite instability
format	article
author	Diana Russo Francisco Mendes
author_facet	Diana Russo Francisco Mendes
author_sort	Diana Russo
title	CTLA-4 blockade in the treatment of colorectal cancer with microsatellite instability
title_short	CTLA-4 blockade in the treatment of colorectal cancer with microsatellite instability
title_full	CTLA-4 blockade in the treatment of colorectal cancer with microsatellite instability
title_fullStr	CTLA-4 blockade in the treatment of colorectal cancer with microsatellite instability
title_full_unstemmed	CTLA-4 blockade in the treatment of colorectal cancer with microsatellite instability
title_sort	ctla-4 blockade in the treatment of colorectal cancer with microsatellite instability
publisher	Shiraz University of Medical Sciences
publishDate	2021
url	https://doaj.org/article/cf9dbae49f62401a8b71557d294ccb74
work_keys_str_mv	AT dianarusso ctla4blockadeinthetreatmentofcolorectalcancerwithmicrosatelliteinstability AT franciscomendes ctla4blockadeinthetreatmentofcolorectalcancerwithmicrosatelliteinstability
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CTLA-4 blockade in the treatment of colorectal cancer with microsatellite instability

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