Distinct impacts of KRAS, NRAS and BRAF mutations on survival of patients with metastatic colorectal cancer.

Wang, Yucai; Loree, Jonathan M.; Yu, Cecilia; Tschautscher, Marcella; Briggler, Andrew M.; Overman, Michael J.; Broaddus, Russell R.; Meric‐Bernstam, Funda; Jones, Jeremy C.; Balcom, Jessica R.; Kipp, Benjamin R.; Kopetz, Scott; Grothey, Axel

doi:10.1200/jco.2018.36.15_suppl.3513

Cited by 12 publications

(12 citation statements)

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“…In a study examining RAS and BRAF mutations, BRAF patients had the worst overall survival. The median OS for WT, KRAS, NRAS and BRAF patients were 49.2, 36.2, 30.1 and 22.5 months, respectively [30]. Similarly, BRAF MT has been shown to be a negative prognostic factor in stage II and III disease.…”

Section: Prognostic Significance Of Braf Mutationmentioning

confidence: 97%

BRAF Mutation and Its Importance in Colorectal Cancer

Luu¹,

Price²

2019

Advances in the Molecular Understanding of Colorectal Cancer

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BRAF mutation is seen in nearly one in ten patients with advanced colorectal cancer. Despite major improvements in survival for advanced colorectal cancer overall, patients with BRAF mutation continue to have a very poor prognosis often with median survival of less than 12 months. It is important for clinicians to be aware of this subgroup as the treatment approach should be different. Treatment options beyond standard chemotherapy are crucial to achieve better outcomes and the role of anti-EGFR therapy alone remains controversial. Current trials assessing combinations of molecular targeted agents have seen some promise. This chapter explores the background of BRAF mutation and current treatment strategies.

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Section: Prognostic Significance Of Braf Mutationmentioning

confidence: 97%

BRAF Mutation and Its Importance in Colorectal Cancer

Luu¹,

Price²

2019

Advances in the Molecular Understanding of Colorectal Cancer

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“…Clinically, BRAF -mutated CRC correlates with poor prognosis and overall survival (OS) in comparison to BRAF wild-type disease [ 119 ]. Furthermore, a study showed that BRAF- mutated CRC patients had worst OS as compared to patients carrying RAS ( KRAS and NRAS ) mutations [ 120 ]. Also, mutation in BRAF is a negative prognostic factor in stage II and III disease [ 121 ].…”

Section: Molecular Basis Of Colorectal Cancermentioning

confidence: 99%

Molecular Mechanisms of Colon Cancer Progression and Metastasis: Recent Insights and Advancements

Malki

ElRuz

Gupta

et al. 2020

IJMS

223

141

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Colorectal cancer (CRC), the third most common type of cancer, is the second leading cause of cancer-related mortality rates worldwide. Although modern research was able to shed light on the pathogenesis of CRC and provide enhanced screening strategies, the prevalence of CRC is still on the rise. Studies showed several cellular signaling pathways dysregulated in CRC, leading to the onset of malignant phenotypes. Therefore, analyzing signaling pathways involved in CRC metastasis is necessary to elucidate the underlying mechanism of CRC progression and pharmacotherapy. This review focused on target genes as well as various cellular signaling pathways including Wnt/β-catenin, p53, TGF-β/SMAD, NF-κB, Notch, VEGF, and JAKs/STAT3, which are associated with CRC progression and metastasis. Additionally, alternations in methylation patterns in relation with signaling pathways involved in regulating various cellular mechanisms such as cell cycle, transcription, apoptosis, and angiogenesis as well as invasion and metastasis were also reviewed. To date, understanding the genomic and epigenomic instability has identified candidate biomarkers that are validated for routine clinical use in CRC management. Nevertheless, better understanding of the onset and progression of CRC can aid in the development of early detection molecular markers and risk stratification methods to improve the clinical care of CRC patients.

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“…BRAF activating mutations, which are usually mutually exclusive with KRAS mutations, represent 5–15% of mCRC, and are associated with a poor prognosis in stage II, III, and IV [ 15 ]. A study performed in 2018 reported a median OS for wild type (wt) KRAS, NRAS, and BRAF mCRC patients of, 49.2, 36.2, 30.1, and 22.5 months, respectively [ 39 ]. The BRAF protooncogene is located in chromosome 7, and is composed of 18 exons; the typical mutation lies on a valine to glutamic acid change at codon 600 (BRAF V600E), corresponding to almost 95% of the mutations observed.…”

Section: Braf Mutations In Colorectal Cancersmentioning

confidence: 99%

BRAF Mutated Colorectal Cancer: New Treatment Approaches

Molina‐Cerrillo

Román

Pozas

et al. 2020

Cancers

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Colon cancer is one of the most frequently diagnosed malignancies in adults, considering both its incidence and prevalence. Anatomically, the right colon is considered as being from the cecum to the splenic flexure, and the left colon is from the splenic flexure to the rectum. Sidedness is a surrogate of a wide spectrum of colorectal cancer (CRC) biology features (embryology, microbiome, methylation, microsatellite instability (MSI), BRAF, aging, KRAS, consensus molecular subtypes (CMS), etc.), which result in prognostic factors. Different molecular subtypes have been identified, according to genomic and transcriptomic criteria. A subgroup harboring a BRAF mutation has been described, and represents approximately 10% of the patients diagnosed with colon cancer. This subgroup has morphological, clinical, and therapeutic characteristics that differ substantially from patients who do not carry this genetic alteration. Unfortunately, there is no established standard of care for this particular cohort of patients. This manuscript aims to study the biology of this subgroup of colon cancer, to understand the current approach in clinical research.

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Distinct impacts of KRAS, NRAS and BRAF mutations on survival of patients with metastatic colorectal cancer.

Cited by 12 publications

References 0 publications

BRAF Mutation and Its Importance in Colorectal Cancer

BRAF Mutation and Its Importance in Colorectal Cancer

Molecular Mechanisms of Colon Cancer Progression and Metastasis: Recent Insights and Advancements

BRAF Mutated Colorectal Cancer: New Treatment Approaches

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