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Article Introduction Colorectal cancer CRC is the third most common cancer in men and the second most common in women.
Although screening, addressability and increased awareness have augmented the number of cases in the non-metastatic setting, approximately one in four individuals with CRC will be diagnosed in stage IV. Additionally, because this improvement in survival has also been associated with substantial health care financial burden, appropriate selection of patients for specific treatments is of utmost importance.
Currently, there are several biomarkers that help clinicians in making the optimal treatment decision: KRAS, NRAS, BRAF mutations, human epidermal growth factor receptor 2 HER2 amplification and microsatellite instability MSI or mismatch repair MMRthey all play a significant role in the process, facilitating selection of the right treatment for the right patient.
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The aim of this review is to provide clinicians with an update on the particular features of these biomarkers. This paper shows the impact of such biomarkers analyzing the results of clinical trials and their outcomes from the perspective of routine clinical practice.
The exclusion criteria were: a articles not within the field of interest of this review: not discussing about clinical, pathological and molecular correlations, predictive factors, prognostic factors of the studied biomarkers; b editorials, letters to the editor, commentaries, conference proceedings; c case reports or small case series; d articles not in English; e studies not in humans.
- Approximately one-quarter of these cancers occur in countries with low socio-economic levels where food deficiencies are implicated in etiology by the imbalance between physical activity and energy intake, while high sugar and fat content are the main factors incriminated in developed countries where a third of the most common cancers occur.
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Figure 1 Flow chart of the search for the eligible studies. KRAS: an indispensable biomarker for anti-epidermal growth factor receptor treatment RAS is a family of proteins expressed in all cell organs belonging to a class of protein called GTPase, and its role is to transmit signals within cells.
These signals finally stimulate cell proliferation.
RAS regulated signal pathways control processes like cell proliferation, cell differentiation, cell adhesion, apoptosis and cell migration. When they are mutated, the cell will have an increased potential of invasion and metastasis.
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Moreover, these are frequently somatic mutations acquired during lifetime. Different KRAS mutations are mainly located in exon 3, codons 59—61, and in exon 4, codons and The distribution of KRAS mutation among clinical trials was Also, in one Middle Eastern study by Zekri et al.
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It is unclear if such geographic and racial variations are due to genetic background or environmental and lifestyle differences. In a meta-analysis by Kafatos et alRAS mutations were distributed almost equally among men and women: Codon 12 mutations were more prevalent in women than in men These studies are limited by the lack of clinical and histological data, as well as by their retrospective observational methodology.
It is a membrane-bound receptor tyrosine kinase and became a key target for monoclonal antibodies advanced prostate cancer forums bind on the extracellular domain of the receptor. The KRAS status is critical for the medical oncologists because it guides the treatment.
Principalele inovatii cu deosebit impact international sunt prezentate pe scurt in cele ce urmeaza 1. Lancet Oncol ;
This may be due to the more frequent activation of EGFR signalling in left-sided tumours compared to those on the right side. This phenomenon is probably due to the heterogeneity of tumours.
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It should also be noted that patients with tumours on the right colon exhibit more frequent BRAF mutations, which result in relative resistance to anti-EGFR treatment. Also, the presence of the KRAS mutation was found to be an independent risk factor for reduced survival. KRAS and NRAS mutant tumours exhibit similar metastasis patterns, namely their dissemination is frequently hepatic, pulmonary and peritoneal.
De Roock et al. Only one of the 13 patients responded to treatment.
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OS depended on the position of the mutation on the exons. It is more common in women older than 70, and for tumours located in the right colon. Thus, regardless of the approach to treatment, median survival is generally reported as 10—16 months shorter in CRC patients with BRAF mutation than in those without it.
In a retrospective study of patients whose secondary hepatic lesions were surgically removed, recurrence-free survival was 5. The results advanced prostate cancer forums these retrospective studies did not reach statistical significance and were insufficient for a definitive conclusion about the potential use of BRAF VE as a biomarker for determining primary resistance to anti-EGFR agents in CRC.
Loupakis et al. HER-2 is located on chromosome 17 and codes a transmembrane protein of kD which is activated through ligand binding.
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Meanwhile, the family of receptors is located on the normal cells; multiple studies have shown that they are overexpressed in multiple malignant tumors, including colorectal cancer. Overexpression of HER2 was not associated with gender and micro-satellite status but was correlated with an aggressive tumoural behaviour which includes profound invasion, lymphatic metastases, distant metastases, perineural invasion and distal colon location with the highest incidence in the rectum.
Two retrospective clinical series supports the idea that HER2 signalling activation could determine cetuximab resistance.
