Colorectal Cancer Modeling with Organoids: Discriminating between Oncogenic RAS and BRAF Variants

Jasmin B Post; Jeanine M L Roodhart; Hugo J G Snippert

doi:10.1016/j.trecan.2019.12.005

Colorectal Cancer Modeling with Organoids: Discriminating between Oncogenic RAS and BRAF Variants

Jasmin B Post, Jeanine M L Roodhart, Hugo J G Snippert

Research output: Contribution to journal › Review article › peer-review

Abstract

RAS and BRAF proteins are frequently mutated in colorectal cancer (CRC) and have been associated with therapy resistance in metastatic CRC patients. RAS isoforms are considered to act as redundant entities in physiological and pathological settings. However, there is compelling evidence that mutant variants of RAS and BRAF have different oncogenic potentials and therapeutic outcomes. In this review we describe similarities and differences between various RAS and BRAF oncogenes in CRC development, histology, and therapy resistance. In addition, we discuss the potential of patient-derived tumor organoids for personalized therapy, as well as CRC modeling using genome editing in preclinical model systems to study similarities and discrepancies between the effects of oncogenic MAPK pathway mutations on tumor growth and drug response.

Original language	English
Pages (from-to)	111-129
Number of pages	19
Journal	Trends in Cancer
Volume	6
Issue number	2
DOIs	https://doi.org/10.1016/j.trecan.2019.12.005
Publication status	Published - Feb 2020

Keywords

RAS
BRAF
CRC
organoids
targeted therapy

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10.1016/j.trecan.2019.12.005

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title = "Colorectal Cancer Modeling with Organoids: Discriminating between Oncogenic RAS and BRAF Variants",

abstract = "RAS and BRAF proteins are frequently mutated in colorectal cancer (CRC) and have been associated with therapy resistance in metastatic CRC patients. RAS isoforms are considered to act as redundant entities in physiological and pathological settings. However, there is compelling evidence that mutant variants of RAS and BRAF have different oncogenic potentials and therapeutic outcomes. In this review we describe similarities and differences between various RAS and BRAF oncogenes in CRC development, histology, and therapy resistance. In addition, we discuss the potential of patient-derived tumor organoids for personalized therapy, as well as CRC modeling using genome editing in preclinical model systems to study similarities and discrepancies between the effects of oncogenic MAPK pathway mutations on tumor growth and drug response.",

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year = "2020",

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T2 - Discriminating between Oncogenic RAS and BRAF Variants

AU - Post, Jasmin B

AU - Roodhart, Jeanine M L

AU - Snippert, Hugo J G

PY - 2020/2

Y1 - 2020/2

N2 - RAS and BRAF proteins are frequently mutated in colorectal cancer (CRC) and have been associated with therapy resistance in metastatic CRC patients. RAS isoforms are considered to act as redundant entities in physiological and pathological settings. However, there is compelling evidence that mutant variants of RAS and BRAF have different oncogenic potentials and therapeutic outcomes. In this review we describe similarities and differences between various RAS and BRAF oncogenes in CRC development, histology, and therapy resistance. In addition, we discuss the potential of patient-derived tumor organoids for personalized therapy, as well as CRC modeling using genome editing in preclinical model systems to study similarities and discrepancies between the effects of oncogenic MAPK pathway mutations on tumor growth and drug response.

AB - RAS and BRAF proteins are frequently mutated in colorectal cancer (CRC) and have been associated with therapy resistance in metastatic CRC patients. RAS isoforms are considered to act as redundant entities in physiological and pathological settings. However, there is compelling evidence that mutant variants of RAS and BRAF have different oncogenic potentials and therapeutic outcomes. In this review we describe similarities and differences between various RAS and BRAF oncogenes in CRC development, histology, and therapy resistance. In addition, we discuss the potential of patient-derived tumor organoids for personalized therapy, as well as CRC modeling using genome editing in preclinical model systems to study similarities and discrepancies between the effects of oncogenic MAPK pathway mutations on tumor growth and drug response.

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KW - BRAF

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KW - targeted therapy

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DO - 10.1016/j.trecan.2019.12.005

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JO - Trends in Cancer

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ER -

Colorectal Cancer Modeling with Organoids: Discriminating between Oncogenic RAS and BRAF Variants

Abstract

Keywords

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