PDF(Pubmed)
Abstract：
UNASSIGNED: Non-small cell lung cancer (NSCLC) with Kirsten rat sarcoma viral oncogene homolog (KRAS) driver alterations harbors a poor prognosis with standard therapies, including chemotherapy and/or immunotherapy with anti-programmed cell death protein 1 (anti-PD-1) or anti-programmed death ligand-1 (anti-PD-L1) antibodies. Selective KRAS G12C inhibitors have been shown to provide significant clinical benefit in pretreated NSCLC patients with KRAS G12C mutation.
UNASSIGNED: In this review, we describe KRAS and the biology of KRAS-mutant tumors and review data from preclinical studies and clinical trials on KRAS-targeted therapies in NSCLC patients with KRAS G12C mutation.
UNASSIGNED: KRAS is the most frequently mutated oncogene in human cancer. The G12C is the most common KRAS mutation found in NSCLC. Sotorasib is the first, selective KRAS G12C inhibitor to receive approval based on demonstration of significant clinical benefit and tolerable safety profile in previously treated, KRAS G12C-mutated NSCLC. Adagrasib, a highly selective covalent inhibitor of KRAS G12C, has also shown efficacy in pretreated patients and other novel KRAS inhibitors are being under evaluation in early-phase studies. Similarly to other oncogene-directed therapies, mechanisms of intrinsic and acquired resistance limiting the activity of these agents have been described.
UNASSIGNED: The discovery of selective KRAS G12C inhibitors has changed the therapeutic scenario of KRAS G12C-mutant NSCLC. Various studies testing KRAS inhibitors in different settings of disease, as single-agent or in combination with targeted agents for synthetic lethality and immunotherapy, are currently ongoing in this molecularly-defined subgroup of patients to further improve clinical outcomes.
UNASSIGNED: In this review, we describe KRAS and the biology of KRAS-mutant tumors and review data from preclinical studies and clinical trials on KRAS-targeted therapies in NSCLC patients with KRAS G12C mutation.
UNASSIGNED: KRAS is the most frequently mutated oncogene in human cancer. The G12C is the most common KRAS mutation found in NSCLC. Sotorasib is the first, selective KRAS G12C inhibitor to receive approval based on demonstration of significant clinical benefit and tolerable safety profile in previously treated, KRAS G12C-mutated NSCLC. Adagrasib, a highly selective covalent inhibitor of KRAS G12C, has also shown efficacy in pretreated patients and other novel KRAS inhibitors are being under evaluation in early-phase studies. Similarly to other oncogene-directed therapies, mechanisms of intrinsic and acquired resistance limiting the activity of these agents have been described.
UNASSIGNED: The discovery of selective KRAS G12C inhibitors has changed the therapeutic scenario of KRAS G12C-mutant NSCLC. Various studies testing KRAS inhibitors in different settings of disease, as single-agent or in combination with targeted agents for synthetic lethality and immunotherapy, are currently ongoing in this molecularly-defined subgroup of patients to further improve clinical outcomes.
摘要：
未经证实：非小细胞肺癌（NSCLC）合并Kirsten大鼠肉瘤病毒癌基因同源物（KRAS）驱动改变的标准疗法预后不良，包括使用抗程序性细胞死亡蛋白1（抗PD-1）或抗程序性死亡配体1（抗PD-L1）抗体的化学疗法和/或免疫疗法。选择性KRASG12C抑制剂已显示在具有KRASG12C突变的预处理的NSCLC患者中提供显著的临床益处。
未经评估：在本次审查中，我们描述了KRAS和KRAS突变肿瘤的生物学特性,并回顾了KRAS靶向治疗KRASG12C突变NSCLC患者的临床前研究和临床试验数据.
未经证实：KRAS是人类癌症中最常见的突变癌基因。G12C是NSCLC中最常见的KRAS突变。Sotorasib是第一个,选择性KRASG12C抑制剂基于先前治疗的显著临床获益和可耐受安全性的证明获得批准，KRASG12C突变的非小细胞肺癌。Adagrasib,KRASG12C的高选择性共价抑制剂，还显示了对预处理患者的疗效，其他新型KRAS抑制剂正在早期研究中进行评估。类似于其他致癌基因导向疗法，已经描述了限制这些药物活性的内在和获得性抗性的机制。
未经批准：选择性KRASG12C抑制剂的发现改变了KRASG12C突变NSCLC的治疗方案。在不同疾病环境中测试KRAS抑制剂的各种研究，作为单一药物或与靶向药物联合用于合成致死性和免疫治疗，目前正在这种分子定义的患者亚组中进行，以进一步改善临床结局。
未经评估：在本次审查中，我们描述了KRAS和KRAS突变肿瘤的生物学特性,并回顾了KRAS靶向治疗KRASG12C突变NSCLC患者的临床前研究和临床试验数据.
未经证实：KRAS是人类癌症中最常见的突变癌基因。G12C是NSCLC中最常见的KRAS突变。Sotorasib是第一个,选择性KRASG12C抑制剂基于先前治疗的显著临床获益和可耐受安全性的证明获得批准，KRASG12C突变的非小细胞肺癌。Adagrasib,KRASG12C的高选择性共价抑制剂，还显示了对预处理患者的疗效，其他新型KRAS抑制剂正在早期研究中进行评估。类似于其他致癌基因导向疗法，已经描述了限制这些药物活性的内在和获得性抗性的机制。
未经批准：选择性KRASG12C抑制剂的发现改变了KRASG12C突变NSCLC的治疗方案。在不同疾病环境中测试KRAS抑制剂的各种研究，作为单一药物或与靶向药物联合用于合成致死性和免疫治疗，目前正在这种分子定义的患者亚组中进行，以进一步改善临床结局。
