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Molecular Profiling of EGFR Status to Identify Skin Toxicity in Colorectal Cancer: A Clinicopathological Review

机译:EGFR状态分子图谱鉴定大肠癌皮肤毒性:临床病理学评论

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摘要

Colorectal cancer (CRC) represents an important health problem, being the third most common type of cancer. In Romania, the CRC incidence has doubled over the years. Both environmental factors and genetic susceptibility are very important for the pathogenesis of CRC. The epidermal growth factor receptor (EGFR) plays an extremely important role in CRC tumorigenesis. Overexpression or dysregulation of EGFR pathway molecules are frequently associated with tumor aggressiveness and patient response to treatment. Based on these considerations, EGFR became one of the first targets of molecular therapies used in CRC. At present, cetuximab and panitumumab are considered to be essential in the treatment of patients with metastatic colorectal cancer expressing the KRAS wild-type gene and EGFR. The main adverse effect for both cetuximab and panitumumab is skin toxicity, present in approximately 80% of patients. The risk of secondary infections, in particular of bacterial infections, is also increased. Cases of staphylococcal infection associated with skin peeling, cellulite, erysipelas, and even Staphylococcus sepsis, were reported. For a long time cutaneous toxicity has been a positive predictor in the efficacy of anti-EGFR treatment, but compliance with treatment and the quality of life of patients with metastatic CRC decreases in the presence of these skin reactions. That is why we emphasize the necessity and importance of using a modern method (molecular analysis of gene polymorphisms possibly supplemented by targeted confocal laser endomicroscopy) to identify a molecular diagnosis, in order to foresee and prevent the appearance of skin reactions and to manage skin toxicity
机译:大肠癌(CRC)代表着重要的健康问题,是第三大最常见的癌症类型。在罗马尼亚,CRC的发病率多年来增长了一倍。环境因素和遗传易感性对于CRC的发病机理都非常重要。表皮生长因子受体(EGFR)在CRC肿瘤发生中起着极其重要的作用。 EGFR途径分子的过表达或失调通常与肿瘤侵袭性和患者对治疗的反应有关。基于这些考虑,EGFR成为CRC中使用的分子疗法的首批靶标之一。目前,西妥昔单抗和帕尼单抗被认为在治疗表达KRAS野生型基因和EGFR的转移性结直肠癌患者中至关重要。西妥昔单抗和帕尼单抗的主要不良反应是皮肤毒性,大约80%的患者存在。继发感染,特别是细菌感染的风险也增加了。据报道有与皮肤脱皮,脂肪团,丹毒甚至葡萄球菌败血症有关的葡萄球菌感染病例。长期以来,皮肤毒性一直是抗EGFR治疗功效的积极预测指标,但是在这些皮肤反应的存在下,治疗顺应性和转移性CRC患者的生活质量下降。这就是为什么我们强调使用现代方法(可能通过靶向共聚焦激光内窥镜检查补充基因多态性的分子分析)来鉴定分子诊断的必要性和重要性,以便预见和预防皮肤反应的出现并管理皮肤毒性

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