结直肠癌治疗的药物基因组生物标志物

Tze-Kiong Er , Luis Bujanda , Maximiliano Rodrigo , Marta Herreros-Villanueva
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引用次数: 1

摘要

结直肠癌(CRC)个体化医疗的一个重要组成部分依赖于使用基于分子生物标志物的最有效治疗,根据特定的肿瘤改变来定义患者群体。因此,抗肿瘤药物被选择性地施用于肿瘤基因改变表明他们在不治疗的情况下复发可能性增加的患者亚组或最有可能对治疗有反应的患者。目前,制药公司在药物开发的早期阶段使用带有生物标志物的靶向药物。然后,根据反应特异性生物标志物开发的伴随诊断允许对正确的患者施用正确的药物。由于结直肠癌已经成为最常见的肿瘤之一,个性化医疗已经改变了肿瘤学家和病理学家的日常工作。事实上,KRAS突变代表了靶向治疗的一场革命,对患者、临床医生和制药公司都有临床意义。然而,新的生物标志物,包括微卫星不稳定性(MSI)和NRAS和BRAF突变,是确定CRC亚组的成熟分子标志物,在讨论治疗方案时应单独考虑。然而,尽管有科学证据,这些生物标志物尚未被纳入实践。为了统一实施,可能需要更多的临床事实和成本效益分析。
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Pharmacogenomic biomarkers for colorectal cancer treatment

An important part of personalized medicine in colorectal cancer (CRC) relies on using the most effective treatment based on molecular biomarkers, which define groups of patients according to specific tumor alterations. Therefore, anti-tumoral drugs are administered selectively to a subgroup of patients whose genetic alterations in the tumors indicate that they have an increased probability of recurrence without treatment or to those patients who will most likely respond to the treatment.

Currently, pharmaceutical companies use targeted drugs with biomarkers during the early stages of drug development. Then, the companion diagnostics that are developed based on response-specific biomarkers allow for the administration of the right drug to the right patient. Because CRC has become one of the most common neoplasias, personalized medicine has changed the oncologists' and pathologists' daily routines. In fact, KRAS mutations represented a revolution in targeted therapies and had clinical relevance for patients, clinicians and pharmaceutical companies. However, the new biomarkers, including microsatellite instability (MSI) and both NRAS and BRAF mutations, are well established molecular markers that determine CRC subgroups and should be considered separately when debating treatment options. However, despite the scientific evidence, these biomarkers have not yet been incorporated into practice. More clinical facts and cost-effectiveness analysis may be needed for their uniform implementation.

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