G13d kras cetuximab. G13D) is the most frequent codon 13 mutation in CRC.

G13d kras cetuximab. Dashed line: mean proliferation, as a percentage of isotype control antibody In conclusion, treatment with cetuximab may be more clinically beneficial in mCRC patients with a KRAS p. G13D. However, recent retrospective studies indicated that patients with tumours mutated in codon 13 of KRAS may benefit from treatment with Cmab in contrast to patients with The primary objective is to determine the 6-month progression free survival (PFS) benefit of cetuximab alone or in combination with irinotecan in patients with KRAS, NRAS, BRAF and PIK3CKA wild type mCRC or KRAS G13D mutated mCRC. Yokota T. Aug 26, 2024 · The anti-tumor activity of this small molecule compound in combination with cetuximab was evaluated using the KRAS G13D mutant CRC models both in vivo and in vitro. Nov 26, 2012 · Other possible limitations were the low frequency and low number of patients in the specific mutant KRAS allelic subgroups, such as in the De Roock et al study 12 which had a total of 32 patients in the KRAS G13D subgroup in pooled analyses of patients in cetuximab monotherapy (n = 10) and cetuximab plus chemotherapy studies (n = 22). Cetuximab treatment significantly reduced the temporal fraction of trapped KRAS WT after stimulation, but only moderately decreased those of KRAS mutants. NRAS/KRAS Resistance Mutations for Panitumumab and Cetuximab in CRC Predicted Response: Primary Resistance Clinical Setting (s): Metastatic (FDA, NCCN, ASCO) Biomarker Criteria: Sample must match one or more of the following: NRAS/KRAS Resistance Mutations for Panitumumab and Cetuximab in CRC Predicted Response: Primary Resistance A study to explore the effects of cetuximab alone or in combination with irinotecan in patients with an abnormal gene (KRAS) in their colon cancer cells. Even more intriguing is a 36% ORR with MK-1084 monotherapy in the phase 1 Kandlelit-001 以上より、化学療法抵抗性の転移を有する大腸癌患者のなかでも KRAS 遺伝子codon 13（p. An assessment of the efficacy and safety of cetuximab-based treatment was performed in an observation-enriched Feb 1, 2011 · The role of the KRAS G13D mutation in patients with metastatic colorectal cancer (mCRC) treated with first-line chemotherapy plus cetuximab. This analysis aims to answer the question of whether first-line treatment of p. These findings indicate that the KRAS p. In xenograft models, KRAS G12D–specific PROTAC degraders have shown the ability to eliminate 95 1. G13D mutation and acquired resistance to cetuximab in colorectal cancer with vulvar metastasis: a case report. from pooled analysis from seven clinical trials [11], and detailed retrospective analysis of colorectal patients with KRAS codon p. The responses observed with the combinatio … Also, the therapeutic efficacy of cetuximab in patients with KRAS mutations remains limited [14], therefore, there is an urgent need to investigate new strategies for targeting metastatic CRC in patients with KRAS G12D mutations. Objective response rates could be improved by additional genotyping of BRAF, NRAS, and PIK3CA exon 20 mutations in a KRAS wild-type population. Özet Background/Aims: Cetuximab is currently approved for the treatment of metastatic colorectal cancer (mCR) with KRAS wild-type. In this study, the cetuximab-resistant KRAS G13D mutation CRC PDX model was induced by repeated use of cetuximab, and the therapeutic e cacy and genomic and transcriptome changes of tumors were dynamically observed in each generation of mice during the treatment process to nd the potential drug resistance mechanism. Dec 1, 2018 · For the KRAS G13D-mutant arm of the ICECREAM study, we reported a similar improvement in 6-month PFS with the addition of irinotecan to cetuximab. Study compared patients with the G13D mutation (allele A, Gly13Asp complemented here to plus chromosomal stand T) receiving chemotherapy (FOLFOX or FOLFIRI) plus cetuximab and those Association of KRAS G13D tumor mutations with outcome in patients with metastatic colorectal cancer treated with first-line chemotherapy with or without cetuximab Excerpt: Jul 9, 2015 · The aim of this retrospective study was to assess the prevalence of KRAS p. Schirripa M et al. May 9, 2025 · Our findings reveal that this HER2-ELF3-KRAS axis is exclusively activated in KRAS G13D, driving aggressive oncogenic features and conferring resistance to cetuximab (CTX) therapy. 2010). G13D-mutated and KRAS wild-type cells were sensitive to cetuximab. Nov 22, 2016 · Conclusion Cetuximab-based treatment seemed to benefit patients with chemotherapy-resistant, refractory KRAS G13D-mutated mCRC. G13D）変異を有する患者は、その他の KRAS 遺伝子変異型患者と比較してcetuximabにより有意な予後改善が得られる可能性が示唆された。 Jun 27, 2012 · Adding cetuximab to first-line chemotherapy appears to provide a benefit to patients with metastatic colorectal cancer with KRAS G13D-mutant tumors. KRAS-WT , KRAS-G12V , and KRAS-G13D cells were serum starved for 18 hours and treated with 2 ng/mL of EGF or 2 ng/mL of EGF (10 minutes) and 0. from publication: Cetuximab treatment for metastatic colorectal cancer RESULTS After treatment with cetuximab or panitumumab, at the optimum concentration of 8 μg/well, the KRAS G13D mutant cell lines HCT-116, LoVo, and T84 showed intermediate sensitivity to both treatments, between the resistant KRAS G12V mutant cell line SW480 and the sensitive KRAS wild-type cell line LIM1215. A mechanism to explain why this mutation behaves differently from other KRAS mutations had long been … Sep 24, 2019 · However, among the various KRAS mutations, that which encodes the G13D mutant protein (KRAS G13D) behaves differently; for unknown reasons, KRAS G13D CRC patients benefit from the EGFR-blocking antibody cetuximab. 5%), G13D (23. Dec 1, 2020 · Phase three clinical trial evidence suggests that colorectal cancers with the KRAS G13D mutation may benefit from EGFR inhibitors, like cetuximab, in contrast to the other most common KRAS mutations. the CACO-2 The KRASG12D variants G12D (37. Nevertheless, retrospective data from large phase III trials led to hypothesize a potential benefit from cetuximab in KRAS G13D mutant pts both in first and advanced lines of treatment (De Roock JAMA 2010, Tejpar JCO 2012). Aug 12, 2024 · The temporal fraction of trapped KRAS G13D increased sharply, and those of KRAS G12D and G12C increased at a moderate rate, while that of KRAS G12V did not elevate after EGF stimulation. In vitro and mouse model data have showed that, although p. 1093/annonc/mdv385. This finding set the stage for one of the first examples of cancer personalized medicine. 38G>A (p. Activating mutations in codon 12, especially G12D, have the highest prevalence across a range of carcinomas and adenocarcinomas. In terms of the microsatellite instability, a recent study implied that cetuximab could even promote disease progression in stage III colon cancer patients with deficient mismatch Response of KRAS G12V, G13D and WT cell lines to (A) 8 g cetuximab treatment and (B) 8 g panitumumab treatment. G12D and p. “The improved survival observed in patients with p. J Clin Oncology. Recently, Tejpar et al. In both DiFi-R and Lim1215-R cells, KRAS amplification or mutations, respectively, were accompanied by increased KRAS activation relative to their parental counterparts. However, in a more recent meta-analysis of 579 CRC patients treated with cetuximab, patients exhibiting the p. We showed that p In conclusion, treatment with cetuximab may be more clinically beneficial in mCRC patients with a KRAS p. Here, we identify honokiol, a small-molecule compound that is specifically sensitive to KRAS G13D CRC cells. G13D Mutations Background: Laboratory research of metastatic colorectal cancer subdivided the disease into a numberof molecular sub-types mainly based on the status of KRAS gene. Nov 5, 2020 · Phase three clinical trial evidence suggests that colorectal cancers with the KRAS G13D mutation may benefit from EGFR inhibitors, like cetuximab, in contrast to the other most common KRAS mutations. G13D mutation and KRAS codon 12 mutations may have a different effect on cetuximab efficacy. The prevalence of the KRAS G13D mutation was significantly higher in patients with AR, and KRAS G13D -mutant patients with AR had a poorer prognosis than those that were negative for the KRAS G13D mutation. Jun 13, 2012 · Sequence analysis of the Lim1215 cetuximab-resistant variants identified acquisition of either KRAS (G13D) or KRAS (G12R) mutations (Fig. Aug 26, 2024 · Meanwhile, there was a reduction in macropinocytosis levels following honokiol and cetuximab co-treated in CRC cells (Figure 2 O-P). These results support the current clinical practice. This study focuses on the role of HER2, a critical prognostic and predictive biomarker, in modulating the unique characteristics of KRASG13D Jan 27, 2025 · Background/Objectives: Colorectal cancer (CRC) remains a leading cause of cancer mortality globally, with KRAS mutations occurring in 30–40% of cases, contributing to poor prognosis and resistance to anti-EGFR therapy. However, retrospective analysis has recently suggested that KRAS-G13D patients can still KRAS G13D Mutation and Sensitivity to Cetuximab or Panitumumab in a Colorectal Cancer Cell Line Model Shalini Sree Kumar,1,2 Timothy J. Sep 27, 2012 · Purpose Targeted therapies using the anti-EGFR antibodies panitumumab (Pmab) or cetuximab (Cmab) are currently restricted to patients with metastatic colorectal adenocarcinoma whose tumours do not show a mutation in KRAS. Although cetuximab may be more clinically beneficial for mCRC patients with KRAS p. ABSTRACT Previous analysis of Phase 3 clinical trial data for colorectal cancer patients treated with cetuximab revealed that patients harboring a KRAS mutation did not benefit from treatment. Cetuximab monotherapy had no activity in patients with metastatic colorectal cancer (mCRC) and KRAS G13D mutations, a finding that contradicts the theory that the G13D mutation differs from other RAS mutations and confers EGFR-1 monoclonal antibody sensitivity. , Celik I. G13D mutations and evaluate the effectiveness of cetuximab in mCRC patients with KRAS p. Jun 25, 2012 · Association of KRAS G13D Tumor Mutations With Outcome in Patients With Metastatic Colorectal Cancer Treated With First-Line Chemotherapy With or Without Cetuximab May 31, 2016 · Discussion: This unique trial will yield prospective information on the efficacy of cetuximab and whether this is further enhanced with chemotherapy in two distinct populations of patients with metastatic colorectal cancer: the "quadruple wild type", which may 'superselect' for tumours sensitive to EGFR-inhibition, and the rare KRAS G13D Oct 15, 2012 · A recent retrospective study in Western countries raised the possibility that KRAS p. Abstract Kristen rat sarcoma (KRAS) gene is one of the most common mutated oncogenes in solid tumors. Among the KRAS variants, the G13D mutation is associated with poor prognosis and distinctive biological behaviors. cmp4 effectively cooperates with compounds Budagyan et al. With inhibitors to KRAS-G12D now entering clinical trials, understanding the biology of KRAS-G12D cancers, and identifying biomarkers that predict therapeutic response is crucial. G13D mutation on cetuximab efficacy in chemotherapy-refractory metastatic colorectal cancer. An assessment of the eficacy and safety of cetuximab-based treatment was performed in an observation-enriched randomized controlled study compar-ing the cetuximab alone group (Cet group) and the combi-nation of cetuximab and irinotecan group (CetI group) for KRAS G13D-mutated mCRC in Japan. Evaluation of cetuximab therapy in these tumors in prospective randomized … Oct 1, 2010 · Association of KRAS p. KRAS mutations are one of most dominant mutations in colorectal cancer (CRC). Of note, we observed that the combination of honokiol (HNK) and cetuximab significantly reduced the viability and proliferation of CRC KRAS G13D cells. In both DiFi-R and Lim1215-R cells, KRAS In particular, G13D mutations seemed to behave differently from other KRAS variants: resistance against Panitumumab-based chemotherapy was observed, but data showed that Cetuximab-based chemotherapy might still improve survival. G13Dmutated tumors may be sensitive to cetuximab and precludes a chemotherapy-driven effect,” the authors wrote. 2010; 304:1812-1820. demonstrate that different KRAS oncogene mutations drive distinct signaling programs in colon adenoma cells. G13D mutation-positive mCRC. We aimed to assess cetuximab monotherapy and cetuximab plus irinotecan in Jul 23, 2020 · However, the mechanism underlying this resistance is incompletely understood. 8%) proteins related CCK-8 the MAPK assay discovered not The results of De Roock et al. Our study demonstrated an association between the presence KRAS G13D mutanted and survival chemotherapy in refractory metastatic colorectal cancer treated with cetuximab. Patients with mCRC and mutation at codon 13 of the KRAS gene do not appear to benefit from treatment with cetuximab. Excerpt: A: Acquired genetic resistance to KRAS G12C within MAPK components can be divided into several classes: (i) mutation of the KRAS G12C codon to another mutant variant (cis G12X) or secondary activating mutations on the trans (previously wildtype) KRAS allele (G12D/R/V, G13D, Q61H) (ii) KRAS switch II pocket mutations that block drug binding (R68 Tejpar S. The present analysis suggests that KRAS codon 12 mutation may not represent a homogeneous entity in mCRC when treated with cetuximab-based first-line therapy. The impact of KRAS mutations on the prognosis and survival of CRC patients drives many research studies to explore potential therapeutics or target therapy for the KRAS mutant CRC. Study showed increased survival for patients with the G13D mutation (allele A, Gly13Asp complemented to plus chromosomal strand = T) compared to those with other codon 13 mutations or mutations in codons 12, 61 or 146 when Dec 14, 2021 · We performed cetuximab dose-response experiments on these cells along with KRAS G13D, G12V, and WT isogenics as controls. Yet, KRAS inhibitors did not follow suit with the development of targeted therapy, for the structure of KRAS has been considered as being implausible to target for decades. Epub 2015 Sep 14. Nov 1, 2021 · SHP2 promotes RAS-driven MAPK signalling, but it is unclear why cancer cells with distinct KRAS mutations exhibit differential sensitivity to SHP2 inhibition. However, studies indicate that not all KRAS mutations are associated with equivalent treatment outcomes. 01 vs. Cetuximab is an epidermal growth factor receptor (EGFR) antagonist, which works by blocking the growth of cancer cells. A phase I trial is currently underway to investigate the role of mRNA-5671/V941, encoding for KRAS G12D, G12V, G12C, and G13D, as monotherapy or combined with pembrolizumab in patients with solid tumors harboring prevalent KRAS mutations (Table 2). These mutations drive tumorigenesis through the constitutive activation of key signaling pathways, such as RAS-RAF-MEK-ERK (MAPK) and PI3K-AKT-mTOR, contributing to therapeutic resistance and poor prognosis. Association of KRAS G13D tumor mutations with outcomes in patients with metastatic colorectal cancer treated with first-line chemotherapy with or without cetuximab [published online ahead of print June 25, 2012]. A mechanism to explain why this mutation behaves Jun 21, 2024 · The targeted therapy adagrasib received accelerated approved for colorectal cancer caused by a mutation called KRAS-G12C, when used in combination with the drug cetuximab. However, recent retrospective studies indicated that patients with tumours mutated in codon 13 of KRAS may benefit from treatment with Cmab in contrast to patients Dec 14, 2021 · In our previous study of KRAS G13D, we demonstrated that sensitivity to cetuximab followed from reductions in WT RAS-GTP (HRAS and NRAS), but not in the mutant KRAS-GTP. G13D mutation or others (n=31). 61-year-old woman Diagnosed with stage IV BRAF V600E CRC in 2022 with metastasis occupying 40% of the liver Following treatment with encorafenib + cetuximab, ctDNA showed BRAF V600E, and newly acquired KRAS G12V, NRAS G13R, NRAS Q61R mutations May 9, 2016 · Association of KRAS G13D tumor mutations with outcome in patients with metastatic colorectal cancer treated with first-line chemotherapy with or without cetuximab Feb 20, 2013 · Computational Analysis of KRAS Mutations: Implications for Different Effects on the KRAS p. Jun 25, 2012 · Conclusion The addition of cetuximab to first-line chemotherapy seems to benefit patients with KRAS G13D–mutant tumors. 2019;98:50 (e18423). We conducted an analysis to study the influence of the KRAS p. Patients with KRAS-G13D-mutated tumours (n = 32) had increased overall survival and progression-free survival compared with those with other KRAS mutations when receiving cetuximab 109. The specific KRAS mutation determines the responsiveness to anti-EGFR monoclonal antibody treatment, corresponding to reported clinical observations. Some researchers suggest that p. However, retrospective analysis has recently suggested that KRAS-G13D patients can still benefit, while only a fraction of KRAS wild-type patients can benefit, from the treatment. Jul 1, 2016 · In patients with G13D-mutated chemotherapy-refractory mCRC, there was no statistically significant improvement in disease control at 6 months with either cetuximab monotherapy or cetuximab plus irinotecan. Association of KRAS G13D tumor mutations with outcome in patients with metastatic colorectal cancer treated with first-line chemotherapy with or without cetuximab. Our results might support the administration of cetuximab-based treatment for KRAS-mutant mCRC and would be able to provide treatment flexibility in this setting. We now compared the efficacy of We report that the tumor suppressor NF1 is comutated in KRAS G13-mutated cells. The treatment of metastatic colorectal cancer (mCRC) includes drugs targeting the epidermal growth factor receptor (EGFR). Sep 12, 2012 · The association of the KRAS p. Methods Associations between tumor KRAS mutation status (wild-type, G13D, G12V, or other mutations) and progression-free survival (PFS), survival, and response were investigated in pooled data from For the KRAS G13D-mutant arm of the ICECREAM study, we reported a similar improvement in 6-month PFS with the addition of irinotecan to cetuximab. May 20, 2011 · Influence of KRAS G13D mutations on outcome in patients with metastatic colorectal cancer (mCRC) treated with first-line chemotherapy with or without cetuximab. Tejpar S, Celik I, Schlichting M, et al. JAMA 2010 May 28, 2021 · Colorectal cancer with a Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) gene mutation is considered to be resistant to anti‑EGFR agents. Jan 15, 2020 · Confusingly, patients with a Glycine to Aspartic Acid mutation at amino acid 13 of KRAS (KRAS G13D) appeared to respond positively to cetuximab, suggesting this mutation is an exception to the rule that KRAS mutations confer resistance to Epidermal Growth Factor Receptor (EGFR) inhibitors. G13D-mutated tumors than with other KRAS-mutated tumors. We observed NRAS Q61K and Q61R cells to show dose-dependent inhibition of proliferation at a level consistent with WT and KRAS G13D isogenic cells (Figure 2 C). Purpose We investigated in the first-line setting our previous finding that patients with chemorefractory KRAS G13D–mutated metastatic colorectal cancer (mCRC) benefit from cetuximab treatment. G13D MUTATION IN PATIENTS WITH METASTATIC COLORECTAL CANCER: A CHEAT IN THE ORCHESTRA OF PREDICTIVE BIOMARKERS? De Roock W, Jonker DJ, Di Nicolantonio F, et al. A recent retrospective study in Western countries raised the possibility that KRAS p. Feb 16, 2022 · However, quite a few studies supported that cetuximab might be effective in KRAS G13D mutation (accounts for approximate 16% of all KRAS mutations) (30, 31). The question of different biological behaviorof atumorand Abstract Background: Cetuximab plus FOLFIRI improved overall survival compared with bevacizumab plus FOLFIRI in KRAS wild-type metastatic colorectal cancer (mCRC) in FIRE-3, but no corresponding benefit was found for progression-free survival. G13D-mutated tumors were as responsive to cetuximab as KRAS wild-type cells [19]. Micro-AbstractCetuximab is currently approved for the treatment of metastatic colorectal cancer with the KRAS wild-type gene. G13D-mutated cells were sensitive, as were KRAS wild type cells (5). Two recent studies have reproduced KRAS G13D specific sensitivity to cetuximab in Micro-AbstractCetuximab is currently approved for the treatment of metastatic colorectal cancer with the KRAS wild-type gene. Most KRAS mutants make it so the patient cannot benefit from the chemotherapy drug, cetuximab; however, patients with the KRAS G13D mutation are exceptions and have appeared to respond to the drug. 2011 ASCO Annual Meeting. Aug 22, 2023 · A mutation in the KRAS gene may affect your treatment options and outlook with colorectal cancer. The authors conducted a systematic review and meta‐analysis to examine whether patients who had metastatic colorectal cancer (mCRC ICECREAM: randomised phase II study of cetuximab alone or in combination with irinotecan in patients with metastatic colorectal cancer with either KRAS, NRAS, BRAF and PI3KCA wild type, or G13D mutated tumours Eva Segelov1*, Paul Waring2, Jayesh Desai3,4, Kate Wilson5, Val Gebski5, Subotheni Thavaneswaran5, Elena Elez6, Craig Underhill7, Nick Pavlakis8, Lorraine Chantrill9,10, Louise Nott11 Dec 1, 2019 · Emergence of KRAS p. and G12C are (2. While confirming the negative effect of KRAS mutations on outcome after cetuximab, we show that BRAF, NRAS, and PIK3CA exon 20 mutations are significantly associated with a low response rate. Apr 11, 2017 · The NORDIC-VII study is a randomised phase III trial of cetuximab plus continuous or intermittent fluorouracil, folinic acid, and oxaliplatin (Nordic FLOX) vs FLOX alone in first-line treatment of A recent retrospective study of cetuximab reported that patients with KRAS p. The study was approved by the Ethics Committee of the Third Affiliated Hospital of Soochow University (Changzhou, China). (B) Similar results were obtained following the administration of panitumumab. The tumors of those patients predominantly had codon 13 mutation, and all codon 13 responder have mutation of p. NF1 GAP protein is inactive against KRAS G12 and Q61-mutated KRAS but stimulates GTP hydrolysis when bound to KRAS G13D. KRAS was knocked-down in KRAS-mutant CRC cells (DLD-1 G13D and SW480 G12V) by small interfering RNAs (siRNA) and overexpressed in KRAS-wild-type CRC cells (COLO320DM) by KRAS-mutant vectors to generate paired CRC cells. Sep 23, 2019 · To understand why KRAS G13D tumors responded to cetuximab, the researchers first used computational models to simulate complex reactions and tease out biochemical differences between healthy and mutant genes based on the biochemical understanding of each process and previous clinical trial data. Aug 1, 2021 · KRAS (kirsten rat sarcoma viral oncogene) is a member of the RAS family. In conclusion, treatment with cetuximab may be more clinically beneficial in mCRC patients with a KRAS p. Nov 1, 2011 · Tejpar S, Bokemeyer C, Celik I, et al: Influence of KRAS G13D mutations on outcome in patients with metastatic colorectal cancer treated with first-line chemotherapy with or without cetuximab. Dec 1, 2012 · Occasionally, some of these patients benefit from treatment with cetuximab, especially patients with a mutation at codon 13. Aug 15, 2023 · KRAS is the most frequently mutated oncogene in cancer. Aug 29, 2011 · De Roock W, Jonker DJ, Di Nicolantonio F, et al. Recently different effect of certain monoclonal antibody (cetuximab) was shown with G13D KRAS mutation against previous data of drug resistance in KRAS mutant tumors. ** P<0. KRAS G13D mutations were observed to account for approximately 16% of all KRAS mutations in advanced colorectal cancer patients, and whether these patients The glycine-to-aspartate transition (p. Methods: A comprehensive analysis of the existing Significance of KRAS G13D in Diseases Colorectal Carcinoma + Malignant Solid Tumor + Non-Small Cell Lung Carcinoma + Pancreatic Carcinoma + Anal Canal Squamous Cell Carcinoma + Breast Carcinoma + Chordoma + Gastric Carcinoma + Glioblastoma + Head And Neck Squamous Cell Carcinoma + Hepatocellular Carcinoma + Malignant Colorectal Neoplasm Feb 20, 2013 · Recently, Tejpar et al. 17 Coupled with the quadruple wild-type data, it appears that true synergy between irinotecan and cetuximab is likely, although we cannot exclude the notion that part of the observed irinotecan Patients who had metastatic colorectal cancer with the v‐Ki‐ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) p. G13D mutation with outcome in patients with chemotherapy-refractory metastatic colorec-tal cancer treated with cetuximab. We conducted a The most common poor prognosis KRAS mutation stably transduced cell lines were into utilized. The authors concluded that patients with KRAS p. Olomorasib is being combined with Erbitux, with the phase 1/2 LOXO-RAS-20001 trial showing a 42% ORR, an apparent improvement over the incumbents. We focus on the combination of AMG-510, the first KRAS G12C inhibitor to receive FDA approval, with cetuximab, the EGFR inhibitor Occasionally, some of these patients benefit from treatment with cetuximab, especially patients with a mutation at codon 13. Oct 10, 2012 · The addition of cetuximab to first-line chemotherapy seems to benefit patients with KRAS G13D-mutant tumors. RESULTS: After treatment with cetuximab or panitumumab, at the optimum concentration of 8 μg/well, the KRAS G13D mutant cell lines HCT-116, LoVo, and T84 showed intermediate sensitivity to both treatments, between the resistant KRAS G12V mutant cell line SW480 and the sensitive KRAS wild-type cell line LIM1215. Phase II study of single-agent cetuximab in KRAS G13D mutant metastatic colorectal cancerAnn Oncol. The aim of this retrospective study was to assess the prevalence of KRAS p. The FDA granted accelerated approval to the KRAS G12C inhibitor adagrasib plus cetuximab for the treatment of colorectal cancer. Design, Setting, and Patients: We studied the association between KRAS mutation status (p. Feb 1, 2014 · • KRAS mutations in codon 13 confers worse prognosis and outcome than those in codon 12. • Cetuximab provides advantage to KRAS G13D patients, mostly due to a higher disease control and PFS. , Sartorius U. G13D mutation showed a significantly longer overall and progression-free survival compared to patients whose tumours were characterised by KRAS mutations in codon 12 (De Roock et al. G13D mutation versus those who had wild-type KRAS tumors. Association of KRAS p. Collectively, these data suggest that the inhibition of autophagy and macropinocytosis fluxes contributes to cytotoxicity of KRAS G13D mutant CRC cells in the presence of cetuximab combined with HNK. drug-free control. However, KRAS mutations typically confer primary resistance to cetuximab due to the uncontrolled activation of the KRAS signaling cascade. Interestingly, the KRAS G13D mutation was also associated with a worse prognosis in the best- supportive-care arm of their study. G13D mutation who received cetuximab [12], indicate that there is no black and white dogma that only mCRC patients with WT KRAS benefit from cetuximab [13]. KRAS^G12D is a frequent genetic mutation not only in colorectal cancer, but also in pancreatic and lung cancer, and the results of thi … May 13, 2020 · KRAS G13D mutations were observed to account for approximately 16% of all KRAS mutations in advanced colorectal cancer patients, and whether these patients can benefit from cetuximab has not been determined. 2b). Conclusions : honokiol enhances the sensitivity of cetuximab by destroying SNX3 retromer in KRAS G13D mutant CRC preclinical model. Aug 14, 2024 · Although KRAS mutations are present in approximately 40% of advanced CRCs, the KRAS G12C mutation only occurs in approximately 3% of patients, whereas KRAS G12D, KRAS G12V, and KRAS G13D are more Apr 26, 2016 · No statistically significant improvement in disease control at 6 months with either single-agent cetuximab or cetuximab plus irinotecan. Annotation of rs112445441 in KRAS Allele T is associated with increased progression-free survival when treated with cetuximab, fluorouracil, irinotecan and oxaliplatin in people with Colorectal Neoplasms. Background: Laboratory research of metastatic colorectal cancer subdivided the disease into a number of molecular sub-types mainly based on the status of KRAS gene. Aug 26, 2024 · Furthermore, we revealed that the synergistic augmentation of cetuximab's sensitivity in vivo and in vitro models of KRAS G13D mutant CRC in combination with honokiol. Targeting ACSS2 selectively sensitizes KRAS G12V cells to downstream inhibition, revealing a therapeutic vulnerability. We conducted a Download scientific diagram | Overall survival curves according to KRAS p. This class of medications allows for targeted degradation of mutant KRAS clones. G13D mutations over patients with KRAS codon 12 mutations. However, a retrospective study reported that a proportion of patients with the KRAS G13D mutation may respond to cetuximab. Through comprehensive analysis of gene expression profiles, we demonstrated that HER2 is a crucial therapeutic target specifically for KRAS G13D CRCs. demonstrated that the addition of cetuximab to first-line chemotherapy appears to benefit patients with KRAS c. An established KRAS G13D mutant colorectal cancer (CRC) patient-derived xenograft (PDX) model was treated with cetuximab. Apr 25, 2016 · RAS mutations predict lack of response to epidermal growth factor receptor monoclonal antibody therapy in patients with metastatic colorectal cancer (mCRC), but preclinical studies and retrospective clinical data suggest that patients with tumors harboring the exon 2 KRAS G13D mutation may benefit from cetuximab. Relative treatment effects were similar to those in patients with KRAS wild-type tumors but with lower absolute values. Preclinical studies in cell lines and xenograft models have demonstrated a response to cetuximab and blockade of the EGFR kinase pathway in the G13D mutants, but not in other (eg G12V) mutants [11]. G13D mutation and acquired resistance to cetuximab in colorectal cancer with vulvar metastasis A case report How to cite this article: Qiang W, Wu Q, Ni X, Zhang C, Zhao J. G13D mutation with outcome in patients with chemotherapy-refractory metastatic colorectal cancer treated with cetuximab. Nov 28, 2012 · We tested our hypothesis that KRAS mutation may be a predictor of oxaliplatin sensitivity in CRC. Patients were included in the CO. The goal of the ICECREAM trial was to investigate and evaluate whether cetuximab should be given alone or in combination with chemotherapy in KRAS wild-type patients. Jan 15, 2020 · The mechanism we revealed involves a cetuximab-mediated reduction in HRAS and NRAS signaling within KRAS G13D cancer cells, owing to impaired binding of KRAS G13D to the tumor suppressor, Neurofibromin (NF1). 0%), G12V (21. Dec 9, 2022 · Recent clinical development of KRAS inhibitors has heightened interest in the genomic landscape of KRAS -altered cancers. G13D mutation and acquired resistance to cetuximab in colorectal cancer with vulvar metastasis: A case report Cetuximab monotherapy had no activity in patients with metastatic colorectal cancer (mCRC) and KRAS G13D mutations, a finding that contradicts the theory that the G13D mutation differs from other RAS mutations and confers EGFR-1 monoclonal antibody sensitivity. G13D mutations. Here the authors show that KRAS Q61H Simulation of the multi-level action mechanism of cmp4 in a computational model describing the Ras activation cycle in conditions designed to represent cells with a constitutively active EGF Receptor, suggests that the compound can work on different Ras oncoproteins, including KRas G13D and KRas G12V. In this study, the patients received a biweekly (500 mg/m 2 on day 1) or weekly (250 mg/m 2) intravenous Nov 15, 2021 · There is growing evidence that KRAS (G12C), KRAS (G12V), KRAS (G12D), and KRAS (G13D) mutations are associated with high PD-L1 expression in lung cancer 100, 101. Annals of oncology : official journal of the European Society for Medical Oncology. G13D Mutation With Outcome in Patients With Chemotherapy-Refractory Metastatic Colorectal Cancer Treated With Cetuximab Kirsten rat sarcoma viral oncogene homolog (KRAS) somatic mutations occur in 30% to 40% of patients with colorectal cancer (CRC). A mechanism to explain why this mutation behaves differently Nov 5, 2020 · Phase three clinical trial evidence suggests that colorectal cancers with the KRAS G13D mutation may benefit from EGFR inhibitors, like cetuximab, in contrast to the other most common KRAS mutations. The combination of MRTX1133 and cetuximab serves as a potential and promising therapeutic approach for colorectal cancer with KRAS^G12D mutation. , Van Cutsem E. G13D) tumors, and the relative treatment effects were similar to those in patients with KRAS wild-type tumors but with lower absolute values [30]. G13D vs other KRAS mutations) and response and survival in a pooled data set of 579 patients with chemotherapy-refractory colorectal cancer treated with cetuximab between 2001 and 2008. PFS is defined as the time from randomisation to disease progression according to RECIST criteria, version 1. Emergence of KRAS p. G13D mutant mCRC were pooled in this analysis. However, because of the limited sample sizes in the current meta-analysis, these results should be interpreted with caution. doi: 10. Lessons: Vulvar metastasis from CRC is relatively rare and indicates a poor prognosis. 2015 Dec;26 (12):2503. Medicine. Confusingly, patients with a Glycine to Aspartic Acid mutation at amino acid 13 of KRAS (KRASG13D) appeared to May 9, 2025 · Colorectal cancer (CRC) is one of the most prevalent cancers worldwide, with KRAS mutations playing a significant role in its tumorigenesis. Prior few studies demonstrated that G13D mutated tumors could benefit from cetuximab. G13D mutation and codon 12 mutations are not created equal in predicting clinical outcomes of cetuximab in metastatic colorectal cancer: a systematic review and meta-analysis. KRAS, Kirsten rat sarcoma 2 viral oncogene homolog; RPR KRAS p. A similar analysis for panitumumab was not as conclusive. These were thought to equally affect prognosis and resistance to anti–epidermal growth factor receptor agents; however, recent data show the activity of KRAS-G12C and pan-RAS inhibitors. G12D is the most common KRAS mutation in colorectal cancer, followed by G12V and G13D. The results showed that treatment with cetuximab was associated with a longer overall and progression-free survival among patients with G13D-mutated tumors when compared with other KRAS -mutated tumors. 5 mg/mL of cetuximab for 24 hours. 1 [18]. According to clinical and basic research data, patients with colorectal cancer exhibiting G12D and G12V KRAS mutations are resistant to anti‑EGFR agents; however Feb 9, 2011 · To the Editor: Dr De Roock and colleagues1 studied the effect of KRAS p. Cetuximab is currently approved for the treatment of metastatic colorectal cancer with the KRAS wild-type gene. A mechanism to explain why this mutation behaves differently from other KRAS mutations had long been lacking. G13D mutation may not be absolutely predictive of non-response compared with other KRAS mutations from the findings of longer overall survival and progression-free survival following cetuximab treatment. Cetuximab may be effective in KRAS G13D mutation patients. KRAS G13D mutant cells also respond to EGFR inhibitors in a neurofibromin-dependent manner. Oct 23, 2008 · Treatment with cetuximab, a monoclonal antibody directed against the epidermal growth factor receptor, improves overall and progression-free survival and preserves the quality of life in patients w Nevertheless, preclinical experiences and retrospective data from large phase III trials suggested that patients carrying KRAS G13D mutation might derive benefit from cetuximab in first and advanced lines of treatment [1–3]. Methods We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate whether the efficacy of anti-EGFR mAbs for mCRC differs between tumours harbouring a KRAS G13D mutation (KRAS G13D) and KRAS mutations other than G13D (other KRAS MT). Apr 25, 2016 · The ICECREAM (Irinotecan Cetuximab Evaluation and Cetuximab Response Evaluation Among Patients with a G13D Mutation) study demonstrates the need to prospectively evaluate hypotheses that were previously supported by retrospective analyses and exemplifies the value of international collaboration in trials of rare molecular subtypes. Outcomes: After an initial response, acquired resistance to cetuximab occurred and vulvar metastasis was established by a second biopsy. Ultimately analysis of KRAS mutation status is required prior to treatment with an anti-EGFR antibody in mCRC with regulating bodies restricting use of panitumumab to patients with confirmed KRAS WT mCRC, and this is unlikely to change unless there is prospective data relating to G13D. Nov 24, 2020 · Cetuximab (brand name Erbitux) is a monoclonal antibody used in the treatment of metastatic colorectal cancer (mCRC) and cancer of the head and neck. Abstract Background KRAS mutations have been characterized as the major predictive biomarkers for resistance to cetuximab treatment. 2015. The same treatment option will also be studied in patients with the KRAS G13D mutation. Aug 26, 2024 · Moreover, honokiol inhibits the conversion of RAS GDP to RAS GTP, heightening the susceptibility of KRAS G13D CRC mutant cells to cetuximab. 18 In pan-creatic cancer, there is a case report of tumor regression after therapy with KRAS G12D speci c TCRs. Jun 18, 2013 · First, regarding KRAS mutation, the efficacy of cetuximab is associated with longer overall and progression-free survival among patients with chemotherapy-refractory colorectal cancer with p. The trial was designed to answer two questions in parallel. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate whether the efficacy of anti-EGFR mAbs for mCRC differs between tu-mours harbouring a KRAS G13D mutation (KRAS G13D) and KRAS mutations other than G13D (other KRAS MT). May 20, 2014 · Mir-31-3p as a predictive biomarker of cetuximab effects in a post hoc analysis of new EPOC phase III trial. Confusingly, patients with a Glycine to Aspartic Acid mutation at amino acid 13 of KRAS (KRAS G13D) appeared to respond positively to cetuximab, suggesting this mutation is an exception to the rule that KRAS mutations confer resistance to Epidermal Growth Factor Receptor (EGFR) inhibitors. 19 Currently, there are fi multiple ongoing early-phase – clinical trials evaluating TCRs in CRC, including NCT0610521 and NCT06043713 for KRAS Feb 15, 2013 · Patients who had mCRC with the KRAS p. G13D-mutated tumors could benefit from anti-epidermal growth factor receptor therapy. Jul 9, 2015 · In conclusion, treatment with cetuximab may be more clinically beneficial in mCRC patients with a KRAS p. Chemotherapy was the initial recommended therapy for KRAS-mutant cancer patients, which was then replaced by or combined May 31, 2016 · The KRAS exon 2 mutation c. Dec 30, 2010 · The in vitro analysis showed that p. G13D mutation in patients with mCRC who were treated with cetuximab. Phase II study of single-agent cetuximab in KRAS G13D mutant metastatic colorectal cancer. G12V-mutated tumors were not responsive to cetuximab, whereas cells from KRAS p. HR, hazard ratio. Dynamic changes in transcription, as determined by WES and RNA sequencing, occurred after repeated drug exposure, and these changes were believed to be the most likely cause of drug resistance. Analysis of RAS / BRAF mutations in a randomized phase II WJOG6510G study of panitumumab plus irinotecan versus cetuximab plus irinotecan in chemorefractory metastatic colorectal cancer. Jun 28, 2024 · KRAS mutations are highly prevalent in a wide range of lethal cancers, and these mutant forms of KRAS play a crucial role in driving cancer progression and conferring resistance to treatment. 38G > A: pGly13Asp (G13D) accounts for ~19 % of KRAS mutations, with an absolute incidence of 8 % in mCRC [11]. Specifically, KRAS G12V cells exhibit unique metabolic dependency on ACSS2 and acetate metabolism for proliferative advantage. Apr 18, 2024 · Recent developments in bioengineering and organic chemistry have enabled targeting of the previously ‘undruggable’ KRAS; this review summarizes the successes, challenges and future of KRAS Jan 1, 2017 · An assessment of the efficacy and safety of cetuximab-based treatment was performed in an observation-enriched randomized controlled study comparing the cetuximab alone group (Cet group) and the combination of cetuximab and irinotecan group (CetI group) for KRAS G13D-mutated mCRC in Japan. Aug 9, 2023 · In conclusion, our findings suggest that co-treatment with 3-BP and cetuximab could be a promising strategy to overcome cetuximab resistance in human CRC. cerevisiae ras2 Δ strain from the pCM184 plasmid, under the Cetuximab, a targeted antibody to Epidermal Growth Factor Receptor (EGFR), has successfully extended overall survival for mCRC patients with wild-type KRAS [5, 6]. Overall survival result and outcomes by KRAS, BRAF, and DNA mismatch repair in relation to primary tumor site in colon cancers from a randomized trial of adjuvant chemotherapy: NCCTG KRAS mutations contributed to anti-EGFR antibody drug resistance in CACO-2 cells. G13D-mutated tumors than with other KRAS-mutated tumors [23]. Jan 6, 2025 · The current study provides insight into the mechanisms of primary resistance to KRAS inhibitors, including aberrant KRAS localization. In this analysis, use of cetuximab was associated with longer overall and progression-free survival among patients with chemotherapy-refractory colorectal cancer with p. A recent retrospective study of cetuximab reported that patients with KRAS p. MSK investigators have led much of the research that resulted in this combined drug approval. Price,3,4 Omar Mohyieldin,5Matthew Borg,4Amanda Townsend,3 To elucidate the role of oncogenic KRAS in autophagy regulation, we expressed FLAG-tagged wild-type KRAS (KRAS WT) or mutated KRAS (KRAS G13D, KRAS G12D and KRAS G12V) in two model systems: in the human non-cancer colon NCM460 cell line, after stable infection, and in the yeast S. THE KRAS p. Mar 3, 2020 · KRAS G13D mutation accounted for about 16% of all KRAS mutations in advanced colorectal cancer patients, and whether these patients can benefit from cetuximab remains controversial. G13D mutations were not shown to benefit from panitumumab therapy in three randomized phase III trials [20]. May 13, 2024 · As a therapeutic class, TCRs have been developed targeting KRAS G12V16,17 and KRAS G12D. Researchers are looking into new treatments that can target KRAS mutations. Oct 27, 2010 · In this analysis, use of cetuximab was associated with longer overall and progression-free survival among patients with chemotherapy-refractory colorectal cancer with p. G13D mutant metastatic colorectal cancer (mCRC) has been identified as representing a cetuximab-sensitive subtype of KRAS mutant mCRC. In particular, cetuximab has anti-proliferative activity in KRAS G13D mutant cell lines and in wild-type ones. G13D) is the most frequent codon 13 mutation in CRC. The effects of uncommon KRAS (uKRAS) variants are largely unexplored. G13D mCRCs should include cetuximab or bevacizumab. Feb 21, 2014 · After treatment with cetuximab or panitumumab, at the optimum concentration of 8 μg/well, the KRAS G13D mutant cell lines HCT-116, LoVo, and T84 showed intermediate sensitivity to both treatments Emergence of KRAS p. Fifty-four patients with p. May 27, 2025 · ASCO will see data from two colorectal KRAS G12C challengers: Lilly’s olomorasib and Merck & Co’s MK-1084. G12V-mutated CRC were insensitive to cetuximab, p. G13D mutation and received cetuximab treatment had better clinical outcomes than patients who had mCRC tumors with KRAS codon 12 mutations. 17, BOND, MABEL, EMR202600, EVEREST, BABEL, or SALVAGE clinical trials or received off Jun 25, 2012 · Conclusion The addition of cetuximab to first-line chemotherapy seems to benefit patients with KRAS G13D–mutant tumors. In this Review, we discuss the Allele T is associated with increased overall survival when treated with cetuximab in people with Colorectal Neoplasms. ) plus cetuximab for adults with KRAS G12C-mutated locally advanced or metastatic colorectal May 13, 2020 · Cetuximab may be effective in KRAS G13D mutation patients. KRAS activating mutations are present in 40% of patients with advanced CRC, and KRAS exon 2 mutations represent the vaster majority of KRAS mutations in CRC. Further molecular analysis showed that the KRAS mutation was detected in plasma samples and tumor tissues. 7%), We and evaluated assessed the the effects activity cells usingmutation drugs using a retrovirus. We showed that p May 13, 2024 · An alternate strategy to target individual KRAS mutations is the development of Proteolysis Targeting Chimeras (PROTACs). , Bokemeyer C. Mar 22, 2019 · [14] Tejpar S, Celik I, Schlichting M, et al. However, there remains a lack of precise information For the KRAS G13D-mutant arm of the ICECREAM study, we reported a similar improvement in 6-month PFS with the addition of irinotecan to cetuximab. KRAS C12D is the most frequent KRAS mutation found in almost 36% of patients followed by KRAS G12V found in 22%, and KRAS G13D present in 15% to 18% of patients. This study aims to investigate whether KRAS G13D mutated tumors benefit from cetuximab in the chemotherapy refractory patients. Abstract Purpose: Targeted therapies using the anti-EGFR antibodies panitumumab (Pmab) or cetuximab (Cmab) are currently restricted to patients with metastatic colorectal adenocarcinoma whose tumours do not show a mutation in KRAS. The KRAS mutation stands out as one of the most influential oncogenic mutations, which directly regulates the hallmark features of cancer and interacts with other cancer-causing driver mutations. However, among the various KRAS mutations, that which encodes the G13D mutant protein (KRAS G13D) behaves differently; for unknown reasons, KRAS G13D CRC patients benefit from the EGFR-blocking antibody cetuximab. No responses were seen with single-agent cetuximab. In addition, we compared the efficacy of cetuximab treatment between patients who had tumors with the KRAS p. G13D or other KRAS mutations. 17 Coupled with the quadruple wild-type data, it appears that true synergy between irinotecan and cetuximab is likely, although we cannot exclude the notion that part of the observed irinotecan Occasionally, some of these patients benefit from treatment with cetuximab, especially patients with a mutation at codon 13. Cells from KRAS p. However, patients with mCRC with KRAS p. G13D-mutated tumors in the cetuximab monotherapy group suggests that p. DLD1 cells with WT (+/−) or KRAS G13D mutant allele were treated with different concentrations of Cetuximab (Cet) or panitumumab (Pab) to study the mechanism underlying the KRAS mutation-induced resistance to anti-EGFR antibodies. Jan 1, 2014 · Results After treatment with cetuximab or panitumumab, at the optimum concentration of 8 μg/well, the KRAS G13D mutant cell lines HCT-116, LoVo, and T84 showed intermediate sensitivity to both treatments, between the resistant KRAS G12V mutant cell line SW480 and the sensitive KRAS wild-type cell line LIM1215. Apr 30, 2025 · Colorectal cancer (CRC) is one of the most common cancers worldwide, with KRAS mutations occurring in approximately 40% of cases. Anti‐EGFR monoclonal antibodies such as cetuximab (CTX) have been approved for the treatment of various malignancies, including colorectal cancer (CRC) with wild‐type KRAS. The role of the <I>KRAS</I> G13D mutation in patients with metastatic colorectal cancer (mCRC) treated with first-line chemotherapy plus cetuximab. G13D mutations had better outcomes compared with those with other mutations. Mutation in codon 12 or 13 in the Kirsten rat sarcoma viral oncogene homolog (KRAS) gene, downstream of the EGFR, evokes May 28, 2019 · Article Open access Published: 28 May 2019 Genetics and Genomics Transcriptional and metabolic rewiring of colorectal cancer cells expressing the oncogenic KRAS G13D mutation Theodosia Charitou Introduction: This study investigated the efficacy and safety of cetuximab-based treatment in patients with chemotherapy-resistant refractory mCRC with KRAS G13D mutation. JAMA. 17Coupled with the quadruple wild-type data, it appears that true synergy between irinotecan and cetuximab is likely, although we cannot exclude the notion that part of the observed irinotecan bene Oct 26, 2015 · ABSTRACT Cetuximab is a standard of care for treating EGFR-expressing metastatic colorectal carcinoma (mCRC) exclusive of those with KRAS mutations at codons 12/13. Feb 1, 2011 · Background: Metastatic colorectal cancer patients with KRAS codon 12 or 13 mutated tumors are presently excluded from treatment with cetuximab (Cmab). G13D-mutated tumors have longer overall survival and progression-free survival than Jun 21, 2024 · On June 21, 2024, the FDA granted accelerated approval to adagrasib (Krazati; Mirati Therapeutics, Inc. It is administered as a weekly intravenous (IV) infusion, but in practice, is often given every other week to coincide with This study investigated the efficacy and safety of cetuximab-based treatment in patients with chemotherapy-resistant refractory mCRC with KRAS G13D mutation. , Schlichting M. Cetuximab is a standard of care for treating EGFR-expressing metastatic colorectal carcinoma (mCRC) exclusive of those with KRAS mutations at codons 12/13. This review explores the biological significance, clinical implications, and therapeutic targeting of KRAS mutations in CRC. . On the other hand, a few patients who have mutated KRAS status occasionally respond to Cmab. G13D mutation appeared to benefit more from cetuximab than patients who had tumors with KRAS codon 12 mutations. We performed a pan-cancer analysis of KRAS -altered samples from 426,706 About ASCO Contact Us Licensing ASCO Overview Press Center Careers at ASCO Mobile Apps Conference Center Rental Association for Clinical Oncology In conclusion, treatment with cetuximab may be more clinically beneficial in mCRC patients with a KRAS p. Sequence analysis of the Lim1215 cetuximab resistant variants identified acquisition of either G13D or G12R KRAS mutations (Fig. However, further investigation is required to clearly determine the benefits of cetuximab treatment in patients with KRAS p. Phase three clinical trial evidence suggests that colorectal cancers with the KRAS G13D mutation may benefit from EGFR inhibitors, like cetuximab, in contrast to the other most common KRAS mutations. G13D mutations compared with those harboring other mutations, further studies are required to elucidate the potential benefits of cetuximab treatment for mCRC patients with KRAS p. (Center for Human Genetics, University of Leuven, Leuven, Belgium). Jul 7, 2022 · KRAS p. compared to patients with other KRAS mutations. Nov 23, 2022 · We investigated the combination of KRAS G12C and EGFR inhibitors. The A recent retrospective study of cetuximab reported that patients with KRAS p. Nov 22, 2016 · This study investigated the efficacy and safety of cetuximab-based treatment in patients with chemotherapy-resistant refractory mCRC with KRAS G13D mutation. G13D mutation with PFS and OS was expressed as a hazard ratio (HR) for patients with p. An assessment of the efficacy and safety of cetuximab-based treatment was performed in an Cetuximab-based treatment seemed to benefit patients with chemotherapy-resistant, refractory KRAS G13D-mutated mCRC. Advances in molecular biology have led to significant In this study, cetuximab-resistance KRAS G13D mutation CRC PDX model was induced by repeated use of cetuximab, and the therapeutic e cacy and genomic and transcriptome changes of tumors were dynamically observed in each generation of mice in the process of treatment to nd the potential drug resistance mechanism. JAMA 2010;304:1812–1820. (A) The RPR with cetuximab administration was significantly elevated in all KRAS G12D, G12V, G13D, G12A, G12C, G12S, Q61H and A146T mutants. Oct 21, 2019 · Approximately 40% of patients with colorectal cancer have a mutated KRAS gene in cells in their tumors. Predictive markers beyond KRAS exon 2 Feb 23, 2015 · KRAS-G12D, G12V, G13D and K117N mediated EGF-independent proliferation, whereas anchorage-independent growth was primarily induced by K117N and Q61H. We conducted a retrospective analysis of 110 patients treated with cetuximab to compare the results according to KRAS mutation status. The question of different biological behavior of a tumor and Mar 3, 2016 · Targeted molecular therapy is an effective anticancer strategy. G13D mutation, compared with those harboring other mutations. Oct 27, 2010 · Design, Setting, and Patients We studied the association between KRAS mutation status (p. vueyy pd3t9l 4eqws kkixk af yv jtmp 43j4 l01 gzl0