Strategies for targeting energy metabolism in Kirsten rat sarcoma viral oncogene homolog ‐mutant colorectal cancer

2018 ◽  
Vol 120 (2) ◽  
pp. 1106-1121
Author(s):  
Gang Wang ◽  
Jun‐Jie Wang ◽  
Pei‐Hao Yin ◽  
Ke Xu ◽  
Yu‐Zhu Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Energy Metabolism ◽  
Viral Oncogene ◽  
Viral Oncogene Homolog

scholarly journals Discovery of a novel and a rare Kristen rat sarcoma viral oncogene homolog (KRAS) gene mutation in colorectal cancer patients

Bioengineered ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 5099-5109
Author(s):  
Mahmood Rasool ◽  
Angel Carracedo ◽  
Abdulrahman Sibiany ◽  
Faten Al-Sayes ◽  
Sajjad Karim ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Gene Mutation ◽  
Kras Gene ◽  
Viral Oncogene ◽  
Colorectal Cancer Patients ◽  
Viral Oncogene Homolog

scholarly journals BRAF and KRAS mutations in metastatic colorectal cancer: future perspectives for personalized therapy

2020 ◽  
Vol 8 (3) ◽  
pp. 192-205 ◽  
Author(s):  
Zi-Nan Li ◽  
Lin Zhao ◽  
Li-Feng Yu ◽  
Min-Jie Wei
Keyword(s):  
Colorectal Cancer ◽  
Clinical Trials ◽  
Survival Rate ◽  
Metastatic Colorectal Cancer ◽  
Early Stage ◽  
Unmet Need ◽  
Growth Factor Receptor ◽  
Kras Mutations ◽  
Viral Oncogene ◽  
Viral Oncogene Homolog

Abstract Colorectal cancer (CRC) is one of the most commonly diagnosed cancers worldwide and 30% of patients with CRC experience metastasis. Patients with metastatic colorectal cancer (mCRC) have a 5-year overall survival rate of <10%. V-raf murine sarcoma viral oncogene homolog B1 (BRAF) and V-Ki-ras2 Kirsten ratsarcoma viral oncogene homolog (KRAS) mutations are mostly studied in mCRC, as clinical trials found that first-line chemotherapy with anti-epidermal growth factor receptor agent confers limited efficacy for mCRC. Treatment decisions for early-stage mCRC do not consider BRAF or KRAS mutations, given the dramatically poor prognosis conferred by these mutations in clinical trials. Thus, it is necessary to identify patients with mCRC harboring BRAF or KRAS mutations to formulate rational therapeutic strategies to improve prognosis and survival. BRAF and KRAS mutations occur in ∼10% and ∼44% of patients with mCRC, respectively. Although the survival rate of patients with mCRC has improved in recent years, the response and prognosis of patients with the aforementioned mutations are still poor. There is a substantial unmet need for prospective personalized therapies for patients with BRAF- or KRAS-mutant mCRC. In this review, we focus on BRAF and KRAS mutations to understand the mechanisms underlying resistance and improving the response rate, outcomes, and prognosis of patients with mCRC bearing these mutations and to discuss prospective personalized therapies for BRAF- and KRAS-mutant mCRC.

scholarly journals Multifunctional Imaging Signature for V-KI-RAS2 Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) Mutations in Colorectal Cancer

2014 ◽  
Vol 55 (3) ◽  
pp. 386-391 ◽  
Author(s):  
K. A. Miles ◽  
B. Ganeshan ◽  
M. Rodriguez-Justo ◽  
V. J. Goh ◽  
Z. Ziauddin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Kras Mutations ◽  
Viral Oncogene ◽  
Viral Oncogene Homolog

scholarly journals Relationship Between 18F-Fluorodeoxyglucose Uptake and V-Ki-Ras2 Kirsten Rat Sarcoma Viral Oncogene Homolog Mutation in Colorectal Cancer Patients

Medicine ◽  
2016 ◽  
Vol 95 (1) ◽  
pp. e2236 ◽  
Author(s):  
Jae-Hoon Lee ◽  
Jeonghyun Kang ◽  
Seung Hyuk Baik ◽  
Kang Young Lee ◽  
Beom Jin Lim ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Viral Oncogene ◽  
18F Fluorodeoxyglucose ◽  
Colorectal Cancer Patients ◽  
Viral Oncogene Homolog

scholarly journals Colorectal Cancer Prognosis is Not Associated with BRAF and KRAS Mutations-A STROBE Compliant Study

2019 ◽  
Vol 8 (1) ◽  
pp. 111 ◽  
Author(s):  
Joon-Hyop Lee ◽  
Jiyoung Ahn ◽  
Won Seo Park ◽  
Eun Kyung Choe ◽  
Eunyoung Kim ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Braf Mutation ◽  
Disease Free Survival ◽  
The Cancer Genome Atlas ◽  
Kras Mutations ◽  
Viral Oncogene ◽  
Mutational Status ◽  
Mutation Group ◽  
Viral Oncogene Homolog

Background: We investigated the associations between v-Raf murine sarcoma viral oncogene homolog B1 (BRAFV600E, henceforth BRAF) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations and colorectal cancer (CRC) prognosis, using The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GSE39582) datasets. Materials and Methods: The effects of BRAF and KRAS mutations on overall survival (OS) and disease-free survival (DFS) of CRC were evaluated. Results: The mutational status of BRAF and KRAS genes was not associated with overall survival (OS) or DFS of the CRC patients drawn from the TCGA database. The 3-year OS and DFS rates of the BRAF mutation (+) vs. mutation (−) groups were 92.6% vs. 90.4% and 79.7% vs. 68.4%, respectively. The 3-year OS and DFS rates of the KRAS mutation (+) vs. mutation (−) groups were 90.4% vs. 90.5% and 65.3% vs. 73.5%, respectively. In stage II patients, however, the 3-year OS rate was lower in the BRAF mutation (+) group than in the mutation (−) group (85.5% vs. 97.7%, p <0.001). The mutational status of BRAF genes of 497 CRC patients drawn from the GSE39582 database was not associated with OS or DFS. The 3-year OS and DFS rates of BRAF mutation (+) vs. mutation (−) groups were 75.7% vs. 78.9% and 73.6% vs. 71.1%, respectively. However, KRAS mutational status had an effect on 3-year OS rate (71.9% mutation (+) vs. 83% mutation (−), p = 0.05) and DFS rate (66.3% mutation (+) vs. 74.6% mutation (−), p = 0.013). Conclusions: We found no consistent association between the mutational status of BRAF nor KRAS and the OS and DFS of CRC patients from the TCGA and GSE39582 databases. Studies with longer-term records and larger patient numbers may be necessary to expound the influence of BRAF and KRAS mutations on the outcomes of CRC.

scholarly journals Undetectable RAS-Mutant Clones in Plasma: Possible Implication for Anti-EGFR Therapy and Prognosis in Patients With RAS-Mutant Metastatic Colorectal Cancer

2020 ◽  
pp. 1070-1079 ◽  
Author(s):  
Mohamed Bouchahda ◽  
Raphael Saffroy ◽  
Abdoulaye Karaboué ◽  
Jocelyne Hamelin ◽  
Pasquale Innominato ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Survival Rates ◽  
Growth Factor Receptor ◽  
Complete Response ◽  
Median Number ◽  
Circulating Tumor Dna ◽  
Survival Times ◽  
Viral Oncogene ◽  
Viral Oncogene Homolog

PURPOSE Combining cetuximab with chemotherapy provides clinical benefit to 60% of the patients with RAS wild-type ( RAS-wt) metastatic colorectal cancer (mCRC). This pilot study investigated the efficacy of cetuximab-based chemotherapy in a sample of patients (40%) with RAS mutation ( RAS-mt) in their primary tumor whose circulating tumor DNA (ctDNA) was RAS-wt. MATERIALS AND METHODS The occurrence of Kirsten rat sarcoma viral oncogene homolog ( KRAS), neuroblastoma rat sarcoma viral oncogene homolog (NRAS), V-raf murine sarcoma viral oncogene homolog B1 ( BRAF), and PI3KCA mutations was determined in ctDNA by using a new ultrasensitive analysis based on mass spectrometry detection. All consenting patients with confirmed RAS-mt mCRC had disease progression on previous chemotherapy that contained no anti–epidermal growth factor receptor (EGFR). The patients with RAS-wt ctDNA received cetuximab + fluorouracil, leucovorin, and irinotecan (FOLFIRI), whereas those with RAS-mt ctDNA were treated with the oncologist’s choice of therapy. RESULTS Of 16 registered patients, 11 were male and five female. They were age 48 to 81 years, and they had unresectable metastatic adenocarcinoma from the colon (n = 11) or rectum (n = 5), with a median of two metastatic sites. They had received a median number of three previous chemotherapy protocols. Plasma genotyping identified RAS-mt in seven patients (44%) and RAS-wt in nine patients (56%). In the patients with wt ctDNA, objective tumor response rate was 50.0%, including one complete response and four partial responses after a median number of 6 courses of cetuximab + FOLFIRI (range, 1 to 16 courses). Two of the nine patients had stable disease, and two had progressive disease. No grade 3 to 4 toxicities were encountered. One-year survival rates were 60.0% for the patients with RAS-wt ctDNA and 17.9% for those with RAS-mt ctDNA. Median overall survival times were not reached and 4.7 months, respectively. CONCLUSION Patients with RAS-mt mCRC whose plasma biopsies contained RAS-wt could benefit from cetuximab-based therapy, a hypothesis to be tested in a prospective randomized trial.

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