Department of Oncology - Pathology, Karolinska Institutet, Sweden; Hellenic Oncology Research Group (HORG), Greece.
University Hospital of Ioannina, Greece.
Crit Rev Oncol Hematol. 2017 Feb;110:1-12. doi: 10.1016/j.critrevonc.2016.12.005. Epub 2016 Dec 9.
Lung cancer remains the leading cause of cancer-related deaths in both men and women. However, the discovery of several oncogenic driver mutations and the development of immune checkpoint inhibitors resulted in improved clinical outcomes for most patients. Although activating KRAS mutations are the most common recurring molecular events in lung adenocarcinoma, little progress has been made during the past decades with no new agents being approved for this indication. The elucidation of the underlying biology of this diverse patient subgroup offers great potential and renewed hope regarding the rational development, rigorous evaluation and subsequent approval of novel targeted agents and combinations which will effectively suppress compensatory escape routes and the emergence of resistance, issues that have plagued previous attempts. Here, we review in a structured manner all aspects of KRAS positive non-small cell lung cancer, including the molecular biology, clinicopathologic characteristics, the prognostic and predictive value of KRAS mutations, as well as previous and contemporary approaches towards the treatment of this elusive target.
肺癌仍然是男性和女性癌症相关死亡的主要原因。然而，几种致癌驱动突变的发现和免疫检查点抑制剂的开发，使大多数患者的临床结果得到了改善。虽然激活的 KRAS 突变是肺腺癌中最常见的复发性分子事件，但在过去几十年中几乎没有取得进展，没有新的药物被批准用于该适应症。对这一多样化患者亚组的基础生物学的阐明，为合理开发、严格评估和随后批准新的靶向药物和联合药物提供了巨大的潜力和新的希望，这些药物将有效地抑制补偿性逃逸途径和耐药性的出现，这些问题一直困扰着以前的尝试。在这里，我们以结构化的方式回顾了 KRAS 阳性非小细胞肺癌的所有方面，包括分子生物学、临床病理特征、KRAS 突变的预后和预测价值，以及以前和当代治疗这一难以捉摸的靶点的方法。
