KRAS exon 3 mutation

EGFR and SMAD4 expression were found to be negatively correlated in GBC tissue samples. ERBB2 overexpression/amplification was observed in 30% of the GBC samples. We also found a low percentage of GBC samples to show KRAS codon 12 mutation in Indian GBC patient population, as had been previously documented in pancreatic cancers.

P3, N=464, Active, not recruiting, GERCOR - Multidisciplinary Oncology Cooperative Group | Recruiting --> Active, not recruiting | Trial completion date: Jun 2021 --> Dec 2024 | Trial primary completion date: Jun 2021 --> Jul 2023

NRAS and BRAF mutations were significantly more frequent in the right colon. BRAF mutation was more common in women and in the right colon.

It provides novel insights into genetic variations specific to the population from Northeastern Romania, which has been underrepresented in previous studies within Eastern Europe. Furthermore, our findings enable the development of genetic profiles in a developing country with limited access to specialized genetic tests and facilitate comparisons with other populations.

P2, N=27, Active, not recruiting, Criterium, Inc. | Recruiting --> Active, not recruiting | Trial completion date: Mar 2023 --> Jan 2025 | Trial primary completion date: Mar 2023 --> Dec 2024

P2, N=93, Completed, AIO-Studien-gGmbH | Active, not recruiting --> Completed

The allele frequency of KRAS mutations in mCRC, assuming a threshold of < 10% for low allele frequency, had no prognostic impact in terms of OS. The study suggests that KRAS mutations in exons 3 and 4 have a negative impact in terms of OS in mCRC.

The first-line therapy consisted of anti-EGFR cetuximab in combination with irinotecan or oxaliplatin-based chemotherapy. PFS2 was statistically significantly shorter for RAS MT patients resulting in statistically non-significantly shorter OS in RAS MT patients. Our findings indicate that a change in RAS status is a negative prognostic factor for the second-line treatment, but this needs to be confirmed in large-scale studies. Testing RAS status analysing ctDNA might help to stratify patients during the metastatic treatment and to personalize the ongoing therapy.

Our prospective observational study revealed not the least proportion of patients with no RAS mutations in ctDNA after 1st- or 2nd-line treatment in RAS mutant mCRC. Further analysis will be performed to evaluate the efficacy of anti-EGFR antibody treatment for patients with no RAS mutation in ctDNA after standard chemotherapy.

Though alterations in the EGFR and ALK genes usually present a favorable prognosis, our work suggests that some of their variants are associated with a poor survival. This study also reveals other mutations like alterations on PIK3CA and CTNNB1 genes, which may impact lung cancer prognosis and will require further exploration.

Patients RASmut on liquid biopsy at baseline are randomized to receive FOLFIRI plus Cetuximab or FOLFIRI plus Bevacizumab... These preliminary data suggest that liquid biopsy might better recapitulate the heterogeneity of mCRC and might be useful in clinical practice to complement tissue testing. The clinical relevance of RAS variants detected in cfDNA will be determined in the LIBImAb trial.

The EBV^(+) subtype was associated with better prognosis. The five-year survival rates were 100.0 and 54.7% for MSI and EBV^(+) GCs, respectively.

In stage I-III CRC patients, KRAS exon 2 mutations had the worst prognosis, whereas KRAS wild type, exon 3 mutations, exon 4 mutations, and NRAS mutations had better prognoses.

Furthermore, identification of the decreased expression or loss of ER/PR in tumors with low-grade histology should prompt consideration of mesonephric-like carcinoma, which is a more aggressive tumor than the low-grade EEC. KRAS mutations were associated with distant metastasis/recurrence in tumors with and without mesonephric-like phenotype.

P2, N=176, Completed, Sun Yat-sen University | Recruiting --> Completed

P2, N=37, Recruiting, Memorial Sloan Kettering Cancer Center

Beside established anti-CRC treatment, better understanding of the causality of CRC can be established by combining epidemiology and genetic/epigenetic on CRC etiology in Morocco. This approach may be able to significantly reduce the burden of disease in the country. Moreover, the Moroccan government should develop policy on CRC prevention and public health programs which may serve as a feasible setting to increase public awareness on lifestyle risk factors.

P2, N=35, Recruiting, Criterium, Inc. | Trial completion date: Dec 2022 --> Mar 2023 | Trial primary completion date: Sep 2022 --> Mar 2023

KRAS mutated CRC patients in North Africa have been identified with incidence closer to the European figures. Beside established anti-CRC treatment, better understanding of the causality of CRC can be established by combining epidemiology and genetic/epigenetic on CRC etiology. This approach may be able to significantly reduce the burden of CRC in North Africa.

Concluding, KRAS G12D and G12C mutations lead to better and worst prognosis, respectively. Further studies are warranted to validate such findings and their possible therapeutic implication.

P1, N=15, Terminated, Boehringer Ingelheim | N=95 --> 15 | Trial completion date: Feb 2024 --> Apr 2022 | Suspended --> Terminated | Trial primary completion date: Jan 2024 --> Apr 2022; Sponsor decision

Although there were no significant differences in survival between patients with exon 2 codon 12 and exon 2 codon 13 mutations, poorer disease-free survival (p=0.085) and overall survival (p=0.005) were seen in those with exon 3 codon 61 mutation than in others. KRAS mutation status was not correlated with survival, but exon 3 codon 61 mutation might be a factor for poor prognosis in patients after resection of CC.

P1, N=95, Suspended, Boehringer Ingelheim | Recruiting --> Suspended

P2, N=34, Completed, Grupo Espanol Multidisciplinario del Cancer Digestivo | Active, not recruiting --> Completed | Trial completion date: Oct 2022 --> Dec 2021

In addition, different prognosis were found among different mutations of KRAS exon2, in detail, worse PFS was showed in CRC patients with KRAS mutation in exon2 G12D than G12V and G13D. Conclusions CRC patients with KRAS mutations in different exons and different site have different genetic and prognostic characteristics, these patients should be managed differently in clinical practice.

However, no correlation could be established between histological malignancy criteria, survival times and the presence of RAS mutations. In summary, canine digital melanoma differs from molecular genetic data of canine oral melanoma and human melanoma, especially regarding the proportion of RAS mutations.

KRAS mutation status was not correlated with survival, but Exon 3 Codon 61 mutation might be a poor prognostic factor in resected CC patients.

P1, N=95, Recruiting, Boehringer Ingelheim | Trial completion date: Dec 2022 --> Feb 2024 | Trial primary completion date: Oct 2022 --> Jan 2024

Systemic examination, extensive immunohistochemistry, and molecular profiling are essential for an accurate diagnosis. More similar cases are required to clarify the biological pathways and even the potential molecular mechanisms of rare lymphomas, which may help direct further treatment.

We report on a large-scale profiling effort to identify mutant alleles that govern radiation survival. Our results reveal new insights into potentially actionable determinants of tumor sensitivity to radiotherapy and accelerate clinical validation of common and rare gene mutations that impact radiation sensitivity.

RAS mutation appears infrequent, and it is not associated with any specific histological phenotype of glioma.

Among KRAS exon 2 mutated patients, codon 13 mutations predict worse prognosis than codon 12 mutations. Mutations of different KRAS exons should be analyzed separately.

Additional analysis of RAS and BRAF mutations could contribute to the selection of patients who are likely to benefit from third-line EGFR inhibitors, regardless of primary tumor location.

P2, N=35, Recruiting, Criterium, Inc. | Trial completion date: Dec 2021 --> Dec 2022 | Trial primary completion date: Sep 2021 --> Sep 2022

P3, N=474, Recruiting, GERCOR - Multidisciplinary Oncology Cooperative Group | Trial completion date: Dec 2019 --> Jun 2021 | Trial primary completion date: Dec 2019 --> Jun 2021

P2, N=34, Active, not recruiting, Grupo Espanol Multidisciplinario del Cancer Digestivo | Recruiting --> Active, not recruiting | Trial primary completion date: Jul 2020 --> Oct 2020

P1, N=95, Recruiting, Boehringer Ingelheim | Not yet recruiting --> Recruiting

P1, N=95, Not yet recruiting, Boehringer Ingelheim

P1, N=7, Completed, NYU Langone Health | Recruiting --> Completed | N=32 --> 7 | Trial completion date: Sep 2020 --> Mar 2020 | Trial primary completion date: Mar 2019 --> Mar 2020