Kras mutation cetuximab. Four of the BRAF mutations were non-V600 variants.

  • Kras mutation cetuximab A cell line from a tumor with a KRAS codon G12V mutation was unresponsive to cetuximab and panitumumab, whereas cell lines from a tumor with a KRAS codon G13D mutation showed an intermediate responsive to cetuximab and DNA samples and KRAS mutation testing. Sreedurgalakshmi, R. G12C single-nucleotide variant (KRAS G12C) is the most frequently reported in NSCLC patients, with a prevalence of about 12–13 %. 18 Several retrospective analyses have clearly demonstrated that activating mutations of KRAS confer resistance to cetuximab therapy in patients with mCRC. Genomic DNA was extracted from primary and metastatic colorectal cancer tissues of patients scheduled to receive cetuximab. Methods. Harikrishnan, Lakshmi Srinivasan and Reena Rajkumari in Technology in Cancer Research & Treatment KRAS G12C mutation is prevalent in ~4% of colorectal cancer (CRC) and is associated with poor prognosis. To examine whether the Kirsten rat sarcoma viral oncogene homolog (KRAS)–variant, a germline mutation in a microRNA-binding site in KRAS, is a predictive biomarker of cetuximab response and altered immunity in the setting of radiotherapy and cisplatin treatment and to evaluate the interaction of the KRAS-variant with p16 status and blood-based KRAS mutation is a predictive biomarker for resistance to cetuximab (Erbitux) in metastatic colorectal cancer (mCRC). Exome sequencing of tumors from patients with progressive disease suggested that microsatellite Mutations in the EGFR extracellular domain (S492R), RAS, and BRAF and amplification of KRAS, HER2, and MET discovered during treatment are associated with secondary resistance to cetuximab . For example, in NSCLC, KRAS mutations account for 20. DNA extraction from FFPE tissue Bei einer Reihe von Tumoren lassen sich Mutationen der RAS (Rat Sarcoma viral oncogene)-Genfamilie nachweisen. 3 months, median progression-free KRAS activating mutations have been reported in 40% of mCRC patients. In colorectal cancer (CRC), KRAS mutations are present in more than 50% of cases, and the KRAS glycine-to sensitize KRAS mutant, cetuximab-resistant cells to cetuximab therapy in vitro and in vivo. However, patients with KRAS mutant genes canno 4-Acetyl-Antroquinonol B Improves the We hypothesized that targeting MEK with selumetinib could overcome resistance to cetuximab in KRAS mutant CRC. Conclusion: The Objective: To explore the relationship between KRAS gene status and efficacy of Cetuximab (C225) combined with chemotherapy on advanced colorectal cancer in Chinese patients, and to evaluate the safety of C225. Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy This study evaluated upfront cetuximab monotherapy in 19 KRAS/NRAS/BRAF mutation-negative CRC patients; 2 (11%) partial responses and 11 (58%) instances of disease stabilization were observed. Tatsächlich bilden HRAS, NRAS und KRAS die am häufigsten Kirsten rat sarcoma viral oncogene (KRAS) mutations make some tumours less responsive to treatment with biological therapies such as cetuximab. V955G, p. It is unknown In summary, the results identify KRAS mutations as frequent drivers of acquired resistance to cetuximab in colorectal cancers, indicate that the emergence of KRAS mutant clones can be detected non-invasively months before radiographic progression and suggest early initiation of a MEK inhibitor as a rational strategy for delaying or reversing drug resistance. Methods: From May 2006 to March 2009, 81 patients with advanced colorectal cancer received Cetuximab combined with chemotherapy were enrolled in this study. 1 months. This study sought to determine if KRAS mutant CRC lines could be sensitized to In cetuximab-sensitive tumours, we identified several mutations in PI3K/AKT and RTK/RAS pathway genes, which would be expected to confer cetuximab resistance, including variants in BRAF, KRAS The incidence of KRAS mutations was in keeping with previous reports. doi: 10. 1–3 Numerous KRAS mutations have been identified thus far, with the most common forms being missense mutations of glycine to aspartic acid at codons 12 (G12D) or 13 (G13D) or glycine to valine at codon 12 (G12V). In our study, 59 patients with a Seit gezeigt werden konnte, dass bei Patienten mit metastasiertem kolorektalem Karzinom (mKRK)eine Mutation im KRAS-Gen mit einem fehlendem Therapieansprechen bei einer Behandlung mit den gegen den Epidermalen KRAS G12C is a mutation that occurs in approximately 3 to 4% of patients with metastatic colorectal cancer. These vary in the specific mutations that they detect, the amount of mutation they detect, the amount of tumour cells needed, the time In KRAS mutant SW-480 cells, RN-PEG-Cet significantly reduced cell viability at lower doses, with an IC50 of 11. A retrospective analysis of early trials of cetuximab therapy suggested that KRAS exon 2 mutation occurs in 27–43% of patients with mCRC tumors, and the reported objective response rate (ORR) was 0 in this group. Cetuximab exerts i Variants in the RAS family (HRAS, NRAS and KRAS) are among the most common mutations found in cancer. In fact, the MGO stress condition recapitulates by itself the features of mutant KRAS resistance to cetuximab and therefore could explain, at least in part, the lack of efficacy of Therefore, if you have a KRAS mutation, you should not receive EGFR inhibitors like cetuximab (Erbitux) or panitumumab (Vectibix). However, further investigation is required to clearly determine the benefits of cetuximab treatment in patients with KRAS p. Therapies targeting the epidermal growth factor receptor (EFGR) are widely used for end-stage CRC. [ 21 ] As of 2008, the most reliable way to predict whether a colorectal cancer patient will respond to one of the EGFR-inhibiting drugs was to test for certain “activating” mutations in the gene that encodes KRAS, which occurs in 30%–50% of Results: A total of 17. Eleven of 309 (4%) KRAS/BRAF evaluable tumors (all KRAS wild type) carried . V955I, and p. K944N) was verified in one of the 27 patients with acquired resistance in a validation cohort, simultaneous KRAS and PIK3CA hotspot In conclusion, treatment with cetuximab may be more clinically beneficial in mCRC patients with a KRAS p. 1 These 3 forms have traditionally constituted >75% of all known KRAS Supplemental material, sj-docx-1-tct-10. G13D mutation-positive mCRC. The ongoing KRYSTAL-1 trial is evaluating the use of adagrasib as monotherapy or in combination with cetuximab in patients with previously treated metastatic colorectal cancer with a KRAS G12C mutation; Adagrasib monotherapy resulted in an objective response rate of 19%, median response duration of 4. Over the past four decades, KRAS has long been considered an undruggable target due to the absence of suitable small-molecule binding sites Recent retrospective evidence from several randomized studies has established that advanced colorectal cancer patients with tumors harboring a mutation in the KRAS gene do not derive benefit from the administration of epidermal growth factor receptor-directed monoclonal antibodies, such as cetuximab or panitumumab. Divarasib, a KRAS G12C inhibitor, has shown modest activity as a single agent in KRAS G12C As of 2006, KRAS mutation was predictive of a very poor response to panitumumab (Vectibix) and cetuximab (Erbitux) therapy in colorectal cancer. 15 Covalent binding of inhibitors in this pocket results in KRAS favoring the 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. 5,6 Subsequent analysis of large RAS family variants—most of which involve KRAS—are the most commonly occurring hotspot mutations in human cancers and are associated with a poor prognosis. Adagrasib, an oral small-molecule inhibitor of mutant KRAS G12C protein, has shown clinical activity in pretreated patients with several tumor types, including colorectal cancer. Of the tumors evaluated for K-ras mutations, 42. A phase I study (NCT01287130) was undertaken to determine the tolerability, and pharmacokinetic profiles of the combination of selumetinib and cetuximab, with an expanded cohort in KRAS-mutant CRC. Methods In a retrospective analysis, 408 patients with confirmed CRC were included, comprising 168 cases in the training set, 111 cases in the internal validation set, and 129 cases in the external Cetuximab, an IgG1 monoclonal antibody targeting the epidermal growth factor receptor (EGFR), has become a component of standard treatment for patients with KRAS wild-type metastatic colorectal cancer. Furthermore, the development of a rash is indicative of cli The predictive value of KRAS mutation in metastatic colorectal cancer (MCRC) patients treated with cetuximab plus chemotherapy has recently been suggested. The aim of this study was to validate, in an independent larger All patients with mutations in KRAS or BRAF failed to respond to cetuximab treatment, and three subjects with NRAS mutations did not respond to cetuximab treatment. The role of KRAS mutations for cetuximab therapy in pancreatic cancer warrants further investigation in larger trials to exclude an epiphenomenon. 17 patient population 9. Cetuximab is a chimeric IgG1 monoclonal antibody (mAb) that targets the extracellular domain of epidermal growth factor receptor (EGFR). 1177_15330338211041453 for Cetuximab–siRNA Conjugate Linked Through Cationized Gelatin Knocks Down KRAS G12C Mutation in NSCLC Sensitizing the Cells Toward Gefitinib by K. Non-FDA-approved uses include colorectal cancer, non-small cell lung cancer (NSCLC), EGFR-expressing, advanced, and BRAF, PIK3CA, KRAS (exons 3 and 4), NRAS, PTEN, and AKT1 mutations were detected in 6, 6, 5, 4, 1, and 1 patient, respectively. 6%), with the highest rate among KRAS mutants in those with G12other mutations (referring to other mutations different from G12C, G12V, G12D, or G12A), and the lowest in those with Q61 mutations. As of 2006, KRAS mutation was predictive of a very poor response to panitumumab (Vectibix) and cetuximab (Erbitux) therapy in colorectal cancer. Biologic tumor characteristics differ on the basis of the KRAS mutation variant. Divarasib plus cetuximab in KRAS G12C- positive colorectal cancer: a phase 1b trial KRAS G12C mutation is prevalent ~%f colorectal cancer (CR) is associated with poor prognosis. 05, Fig. Divarasib, a KRAS G12C inhibitor, has shown modest activity as a single agent in KRAS G12C Adagrasib, an irreversible, selective KRAS G12C inhibitor, may be an effective treatment in KRAS G12C-mutated colorectal cancer, particularly when combined with an anti-EGFR antibody. Mutation in KRAS is a primary mechanism of cetuximab resistance and is found in 30-40% of patients with mCRC . While the FDA label The KRAS gene is mutated in approximately 40% of CRCs, the most frequent mutations occurring at codons 12 (G12D, 13%; G12V, 9%) or 13 (G13D, 8%). In tumors with only KRAS mutations, RAS mutant metastatic colorectal cancer (mCRC) patients are excluded from treatment with anti-epidermal growth factor receptors. [ 21 ] As of 2008, the most reliable way to predict whether a colorectal cancer patient will respond to one of the EGFR-inhibiting drugs was to test for certain “activating” mutations in the gene that encodes KRAS, which occurs in 30%–50% of Objectives. It is important to note that the mutation rate of KRAS in the pancreas was 67. One subject with a low NRAS G12C mutant allele frequency (5%) did show a The 2018 FDA-approved drug label for cetuximab states that for mCRC, cetuximab is indicated for K- and N-RAS wild-type (no mutation), EGFR-expressing tumors. Key findings. 2012 Jun 28;486(7404):532-6. This study sought to determine if KRAS mutant CRC lines could be sensitized to cetuximab using dasatinib (BMS-354825, Sprycel), a potent, orally bioavailable inhibitor of several tyrosine kinases, including the Src family kinases (SFKs). K944N, p. Increasing evidence from different The KRAS mutations often lead to constitutive activation of the mitogen-activated protein kinase Increased Mortality, or Lack of Benefit in Patients with Ras- Mutant mCRC. Epidermal growth factor receptor has been recognized as a major upstream activat Divarasib plus cetuximab in KRAS G12C-positive colorectal cancer: Cetuximab-resistant oral squamous cell carcinoma cells become sensitive in Detection of Low-Abundance KRAS Mutations in Colorectal Cancer Using Microfluidic Capillary Electrophoresis -Based KRAS mutation in codon 12 may be associated with reduced survival compared to KRAS wild type. We assessed whether the mutation status of the K-ras gene was associated with survival in the cetuximab and supportive-care groups. 001 for the interaction of K-ras mutation status with overall survival Detection of Low-Abundance KRAS Mutations in Colorectal Cancer Using Microfluidic Capillary Electrophoresis-Based Restriction Fragment Length Polymorphism Fifty-three wild-type KRAS exon 2 mCRC patients were treated with cetuximab/irinotecan-based chemotherapy as a first- or third-line therapy. 1038/nature11156. The label states that an FDA-approved test must be used to confirm the absence of a RAS mutation (in either KRAS or NRAS) prior to starting cetuximab (Table 1) (1). Cetuximab is an epidermal growth factor receptor (EGFR) inhibitor with the following FDA-approved indications: colorectal cancer, metastatic, KRAS wild-type (without mutation), and head and neck cancer (squamous cell). The mutational statuses of 10 EGFR pathway Eighty-nine metastatic CRC patients treated with cetuximab after treatment failure with irinotecan-based chemotherapy were analyzed for KRAS mutation by allelic discrimination Analysis of metastases from patients who developed resistance to cetuximab or panitumumab showed the emergence of KRAS amplification in one sample and acquisition of secondary Interestingly, in contrast to tumor acquired KRAS mutations which predict cetuximab resistance, patients with the KRAS-variant have repeatedly been shown to respond We investigated the efficacy of cetuximab plus irinotecan, fluorouracil, and leucovorin (FOLFIRI) as first-line treatment for metastatic colorectal cancer and sought We previously showed that KRAS mutations were associated with resistance to cetuximab in 30 CRC patients. Compared to free Cet, RN-PEG-Cet demonstrated a ~ 2-fold increase These findings highlight that KRAS/BRAF mutations lead to the downregulation of FOXO3a and contribute to cetuximab resistance in CRC cells with KRAS/BRAF mutations. Cetuximab, a monoclonal antibody that binds the extracellular domain of EGFR, is effective in a subset of KRAS wild type metastatic colorectal cancers 1. Your doctor may choose a different cancer treatment like Purpose To establish a CT-based radiomics nomogram for preoperative prediction of KRAS mutation and prognostic stratification in colorectal cancer (CRC) patients. Oncogenic KRAS mutations in tumors have been shown to be a negative predictor of the response of colorectal cancer (CRC) to cetuximab treatment. . As a single agent and in combination with cytotoxic agents, cetuximab has been shown to improve overall survival, when compared to placebo or standard of care, in patients with metastatic KRAS and NRAS exon 2–4 wild-type (WT) colorectal cancer (CRC) [1,2,3]. However, there was a time-dependent effect of cetuximab seen only in KRAS-variant patients—while the hazard of death was higher in cetuximab-treated patients within year 1 [HR = 3. For many Anti-EGFR antibodies such as cetuximab are active against KRAS/NRAS wild-type colorectal cancers (CRCs), but acquired resistance invariably evolves. 4% of KRAS, and the dominant substitution is G12C (glycine (GGT) to cysteine (TGT)), while KRAS mutation accounts for up to 67. Several clinical trials demonstrated that mutated KRAS and BRAF genes are predictive markers of outcomes in mCRC treatment (). Erst seit Anfang 2020 steht der spezifische und irreversible KRAS-Inhibitor Sotorasib für den Context Patients with metastatic colorectal cancer who have KRAS codon 12– or KRAS codon 13–mutated tumors are presently excluded from treatment with the anti–epidermal growth factor receptor monoclonal antibody Also, KEAP1 mutations were more frequent in KRAS-mutant tumors, especially in those with G13 mutations, while TP53 mutations were more frequent in KRAS WT NSCLC (73. Cetuximab is not indicated for the treatment of patients with CRC that harbor somatic mutations in exon 2 (codons 12 and 13), exon 3 (codons 59 and 61), and exon 4 Summary. KRAS mutation is a predictive biomarker for resistance to cetuximab (Erbitux) in metastatic colorectal cancer (mCRC). De Roock W, Claes B, Bernasconi D, De Schutter J, Biesmans B, Fountzilas G, et al. Das BRAFV600E-mutierte mCRC ist daher besonders schnell progredient, das Gesamtüberleben im Vergleich zum Wildtyp um etwa die Hälfte reduziert. (A) Western blot analysis of expression of p-EGFR/EGFR in CRC cells. About 19% patients with cancer harbor RAS mutations, which are typically associated with poor clinical outcomes. 6% K ras mutations are present in 33% to 40% of cases of colorectal cancer (CRC). In a co-clinical murine trial, cohorts of genetically engineered mice with either KRAS, KRAS and p53 (KRAS/p53) or KRAS/LKB1-mutant lung cancers were generated. Divarasib, a KRAS The current study focused on minor KRAS mutations (G12A, G12C, G12S, Q61H and A146T) and evaluated whether these were resistant to anti‑EGFR antibodies using a Somatic KRAS mutations occur in approximately half of the patients with metastatic colorectal cancer (mCRC). In addition to the trials discussed above, the table includes several trials that indicate the predictive effect of BRAF and KRAS mutations [18, 31, 34, 46, 48–52]. These data support a potential new Kristen rat sarcoma viral oncogene homolog (KRAS) mutations play a major role in the carcinogenesis of many types of solid tumors including non-small cell lung cancer (NSCLC). To examine whether the Kirsten rat sarcoma viral oncogene homolog (KRAS)–variant, a germline mutation in a microRNA-binding site in KRAS, is a predictive biomarker of cetuximab response and altered immunity in the setting of radiotherapy and cisplatin treatment and to evaluate the interaction of the KRAS-variant with p16 status and blood-based Kirsten rat sarcoma virus oncogene homolog (KRAS) is the most frequently mutated oncogene in human cancer. (B,C) Cell proliferation analysis by using sulforhodamine B (SRB) assay of KRAS-wild (Caco-2) and KRAS-mutant CRC cell lines. A main limitation of therapies that selectively target kinase signaling pathways is the emergence of secondary drug resistance. For almost four decades, KRAS has Purpose: Cetuximab is efficient in advanced colorectal cancer (CRC). The aim of this study was to validate, in an independent larger series of 89 patients, the prognostic value of KRAS mutations on response to cetuximab and survival. As a result, we found that the anti-growth inhibitory effect of GC1118 was more obviously in KRAS wild-type cell lines, SNU-719 and MKN-45, but also in KRAS mutant SNU-601 cells (p < 0. After an initial response, secondary resistance invariably ensues, thereby limiting KRAS mutation is a predictive biomarker for resistance to cetuximab (Erbitux) in metastatic colorectal cancer (mCRC). Importantly, in KRAS G12C-mutant cancers, the mutant cysteine at position 12 is in proximity to the nucleotide pocket and switch regions. These trials clearly demonstrated that the mutation statuses of BRAF and KRAS were The inhibition of ERK signaling was found to assist in reducing PD-L1 expression through autophagy in intrahepatic cholangiocarcinoma (iCCA), indicating that ERK-targeted therapy may be combined with anti-PD-(L)1 immunotherapy for KRAS-mutant iCCA . Despite its success in metastatic colorectal cancer trials, the effectiveness of cetuximab for treating early stage disease is uncertain; adjuvant Of 315 KRAS evaluable patient samples (93%), 179 tumors (57%) were KRAS wild type. G13D mutations and Objectives. KRAS mutations are known to Cetuximab reduced the efficacy of oxaliplatin when administered before oxaliplatin but provided additive effect when administered after oxaliplatin regardless of the KRAS or BRAF mutation status Cetuximab plus FOLFIRI in first-line treatment of KRAS mutation-negative, EGFR-positive metastatic colorectal cancer See Commentary on Page 302 I n July 2012, cetuximab was approved for use in com-bination with FOLFIRI (irinotecan, 5-fluorouracil, leucovorin) for first-line treatment of patients with KRAS mutation-negative (wild-type), EGFR The KRAS mutation is one of the leading driver mutations in colorectal cancer (CRC), and it is usually associated with poor prognosis and drug resistance. 1% (56/328) of patients had the KRAS-variant, and overall survival rates were similar between KRAS-variant and non-variant patients. F930S, p. The cycling of mutant KRAS between active and inactive forms enables targeting of the inactive GDP-bound state. Equipping cetuximab on the surface of NK cells may solve the problem of cetuximab resistance in To compare the anti-tumor effects of GC1118 with those of cetuximab, we conducted an MTT assay by comparing cell numbers on days 1, 3, and 5. Results Previous reports have shown that PIK3CA mutations can confer acquired resistance to KRAS G12C inhibitor and KRAS G12C inhibitor–cetuximab combination therapy in patients with NSCLC and CRC 34,35 Functional studies showed that novel PIK3CA mutations (all in exon 19; p. 28,29 There was an interaction between treatment group and KRAS status for the response to KRAS G12C mutation is prevalent in ~4% of colorectal cancer (CRC) and is associated with poor prognosis. 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]. 1b). However, upon cetuximab treatment, further liver relapse occurred, and two KRAS mutations at codon 13 and 12 were detected in the metachronous liver metastatic tissues. Four tumors harbored multiple co-existing (complex) mutations. 01 and P<0. G13D mutation, compared with those harboring other mutations. All patients with BRAF mutations or complex mutation patterns were cetuximab non-responders. The activation of KRAS G12D and inactivation of p53 or LKB1 in the lung epithelium was attained using nasal instillation of adenovirus encoding the CRE recombinase. 6% of KRAS in pancreatic adenocarcinoma, and KRAS (G12D) is the dominant mutant subtype. Srikar, K. All Intriguingly, when MRTX1133 was used in combination with cetuximab, KRAS G12D-mutant colorectal cancer growth was effectively inhibited, both in vitro and in vivo. K966E) promote cell viability in the presence of cetuximab. Divarasib, a KRAS G12C inhibitor, has shown modest activity as a single agent in KRAS G12C-positive CRC at 400 mg. In this analysis of the KRYSTAL KRAS G12C mutation is prevalent in ~4% of colorectal cancer (CRC) and is associated with poor prognosis. Furthermore, we also assessed Published in Cancer Discovery, 1 the study showed a 34% response rate among 94 patients with KRAS G12C-mutated CRC treated with the combination of adagrasib (an irreversible agent that blocks the KRAS Cetuximab is a monoclonal antibody that targets the epidermal growth factor receptor (EGFR). Median time to progression approached 6. Among KRAS mutations, p. Four of the BRAF mutations were non-V600 variants. We previously showed that KRAS mutations were associated with resistance to cetuximab in 30 CRC patients. This combina-torial therapy led to altered signaling in: (1) components of the MAPK pathway, (2) the b KRAS-Mutationen gelten bei vielen Tumorerkrankungen als Treiber für die unkontrollierte Zellteilung. There are a variety of tests available to detect these mutations. 7%) cases. 37, 95% confidence Adagrasib plus cetuximab demonstrates promising clinical activity and tolerable safety in heavily pretreated patients with unresectable or metastatic KRAS G12C-mutated colorectal cancer. 7 µg/mL at 72 h. Only patients with tumors that expressed wild-type KRAS responded to cetuximab—an objective response was In this case, no KRAS mutation was detected in the primary or metastatic tumor samples before the beginning of the cetuximab treatment. Authors Sandra Misale 1 , Among a series of 113 patients, KRAS mutations were identified in 46 (40. Monotherapy with KRAS G12C inhibitors has yielded KRAS mutation and response to treatment with cetuximab plus chemotherapy We detected a KRAS mutation by sequencing analysis of DNA extracted from tumour sample in 16 out of 59 (27%) patients KRAS-mutated CRC cells resist cetuximab treatment. Development of KRAS G12C Inhibitors. 3% had at least In this study, tumors from 30 metastatic colorectal cancer patients treated by cetuximab were screened for KRAS, BRAF, and PIK3CA mutation by direct sequencing and The effectiveness of cetuximab was significantly associated with K-ras mutation status (P=0. Only one novel PIK3CA mutation (p. Mutation mit raschem Fortschreiten assoziiert. 10 Previous comparisons between patients with KRAS wild-type tumors and those with KRAS mutations have not differentiated between the mutational subtypes. The graphic represents the dose-dependent and time-dependent effect of cetuximab on the relative cell proliferation of CRC With the accumulating evidence demonstrating the ineffectiveness of anti-EGFR in patients with KRAS mutations, the study group undertook correlative analyses to determine whether the mutation status of the KRAS gene modified the effect of cetuximab on the overall survival (OS) and PFS in the CO. In a large, retrospective pooled exploratory analysis of patients with chemotherapy-refractory colorectal cancer, we show for the first time that there is a positive association between KRAS p. 5, 19, 20 Given the results of these analyses, the use of cetuximab has been restricted to mCRC patients with wild-type KRAS Cetuximab, a monoclonal antibody that binds the extracellular domain of epidermal growth factor receptor (EGFR), is effective in a subset of KRAS wild-type metastatic colo Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer Nature. 4 These reports also established superior ORRs with EGFR inhibitors in wild-type (WT) KRAS tumors. pgeaig lkck wygeax jpjfmtv yiej ktsd iwmk nvuwfi yljzc dhr