KRAS, NRAS, BRAF, HER2 and microsatellite instability in metastatic colorectal cancer – practical implications for the clinician

Afrăsânie, Vlad-Adrian; Marinca, Mihai Vasile; Alexa-Stratulat, Teodora; Gafton, Bogdan; Păduraru, Marius; Adavidoaiei, Anca Maria; Miron, Lucian; Rusu, Cristina

doi:10.2478/raon-2019-0033

Cited by 108 publications

(89 citation statements)

References 90 publications

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“…BRAF-mutated CRC is currently receiving attention not only from clinicians, but also basic scientists, and thus numerous reviews have been published [3,[8][9][10][11][12][13][14][15][16]. As a medical oncology team, we would like to highlight BRAF-mutated CRC from the clinician's viewpoint.…”

Section: Introductionmentioning

confidence: 99%

BRAF Mutation in Colorectal Cancers: From Prognostic Marker to Targetable Mutation

Nakayama

Hirota

Shinozaki

2020

Cancers

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The Raf murine sarcoma viral oncogene homolog B (BRAF) mutation is detected in 8–12% of metastatic colorectal cancers (mCRCs) and is strongly correlated with poor prognosis. The recent success of the BEACON CRC study and the development of targeted therapy have led to the determination of BRAF-mutated mCRCs as an independent category. For nearly two decades, a growing body of evidence has established the significance of the BRAF mutation in the development of CRC. Herein, we overview both basic and clinical data relevant to BRAF-mutated CRC, mainly focusing on the development of treatment strategies. This review is organized into eight sections, including clinicopathological features, molecular features, prognosis, the predictive value of anti-epidermal growth factor receptor (EGFR) therapy, resistant mechanisms for BRAF-targeting treatment, the heterogeneity of the BRAF mutation, future perspectives, and conclusions. A characterization of the canonical mitogen-activated protein kinase (MAPK) pathway is essential for controlling this malignancy, and the optimal combination of multiple interventions for treatments remains a point of debate.

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Section: Introductionmentioning

confidence: 99%

BRAF Mutation in Colorectal Cancers: From Prognostic Marker to Targetable Mutation

Nakayama

Hirota

Shinozaki

2020

Cancers

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“…Molecular markers such as K-Ras, N-Ras, B-Raf, HER2, and MSI play a signi cant role in the disease prognosis in CRC, and hence, analysis of these biomarkers helps in facilitating proper treatment to the needy patients [30]. In our study, all the patients in MSI-H status survived for > 3 years, while 3year OS of patients in MSS status was only 35.0% (P = 0.047).…”

Section: Discussionmentioning

confidence: 58%

En Bloc Right Hemicolectomy with Pancreaticoduodenectomy for Locally Advanced Right-Sided Colon Cancer

Yan¹,

Wang²,

Bao³

et al. 2020

Preprint

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Background: En bloc right hemicolectomy with pancreaticoduodenectomy (RHCPD) is the optimum treatment to achieve the adequate margin of resection (R0) for locally advanced right-sided colon cancer (LARCC). Information regarding the indications and outcomes of this procedure is limited.Method: In this retrospective study, patients who underwent RHCPD for LARCC during October 2010 to May 2019 were identified. The overall survival (OS), disease-free survival (DFS), mortality, postsurgical complications, gene mutational analysis, and prognostic factors were evaluated. Survival was estimated using Kaplan-Meir method.Results: Nineteen patients who underwent RHCPD were included in the study. The OS was 88.2%, 65.9%, and 57.6% at 1, 3, and 5 years. The DFS was 71.6%, 56.4%, and 56.4% at 1, 3, and 5 years. The median operative time was 320 minutes (range: 222-410 minutes), and the median operative blood loss was 268 mL (range: 100-600 mL). The OS was significantly better among patients with well-differentiated tumor (P=0.03), N0 stage (P=0.01), and high microsatellite instability (MSI) (P=0.047) and in patients who received chemotherapy (P=0.027). The major postoperative complications occurred in 8 patients (42%), with pancreatic fistula (PF) being the most common. On the basis of the univariate analysis, poorly differentiated tumor, regional lymph node dissemination, MSI status, and no perioperative chemotherapy were the significant predictors of poor survival (P<0.05). By multivariate analysis, only lymph node status was the significant factor (hazard ratio [HR]: 79.045; P=0.021).Conclusions: This study suggests that RHCPD is feasible and can achieve complete tumor clearance with favorable outcome, particularly in patients with lymph node-negative status.

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“…3A). KRAS and BRAF mutations are valuable clinical biomarkers used to guide CRC patient treatment [37]. In this study, we found that almost all patients with KRAS mutations yielded MSS samples that clustered in the Immunity_L subgroup, whereas the majority of samples with BRAF V600E mutations were MSI samples in the Immunity_H subgroup (Fig.…”

Section: Assessment Of Immune Checkpoint Marker Expression and The Tumentioning

confidence: 68%

Identified and Validated the Characterization of the Colorectal Cancer Tumor Immune Microenvironment

Han¹,

Chen

Yang³

2020

Preprint

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Background While the administration of immunotherapy can facilitate the development of durable anti-tumor immunity in certain colorectal cancer (CRC) patients.This study was therefore designed to conduct a robust analysis of the CRC immune microenvironment to identify specific genes and pathways that can be targeted in an effort to achieve more effective immunotherapy outcomes. Methods Using five Independent data sets, we analyzed expression profiles associated with 29 different immune signatures, and we used these profiles to guide the hierarchical clustering of CRC samples based on their immune microenvironmental composition. Results We were able to cluster our CRC samples based on whether they had exhibited high, medium, or low levels of infiltration by immune cell types associated with tumor clearance (Immunity_H, Immunity_M, and Immunity_L, respectively). Samples in the Immunity_H subset exhibited a “hot” immune microenvironment, with higher stromal scores, higher immune scores, and lower tumor purity. The microsatellite instability (MSI) group included the majority of the Immunity_H samples, whereas most Immunity_M and Immunity_L samples were incorporated into the microsatellite stability (MSS) .The vast majority of patients with KRAS mutations were in the Immunity_L and MSS groups, whereas the majority of patients exhibiting BRAF V600E mutations were found in the Immunity_H and MSI-H samples. TMB high samples included a majority of the Immunity_H samples and a small subset of the Immunity_M samples. Conclusions Our results identify three reproducibly validated immune subtypes of CRC tumor samples, potentially offering valuable insights that may guide the immunotherapeutic treatment of these patients.

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KRAS, NRAS, BRAF, HER2 and microsatellite instability in metastatic colorectal cancer – practical implications for the clinician

Cited by 108 publications

References 90 publications

BRAF Mutation in Colorectal Cancers: From Prognostic Marker to Targetable Mutation

BRAF Mutation in Colorectal Cancers: From Prognostic Marker to Targetable Mutation

En Bloc Right Hemicolectomy with Pancreaticoduodenectomy for Locally Advanced Right-Sided Colon Cancer

Identified and Validated the Characterization of the Colorectal Cancer Tumor Immune Microenvironment

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