Advances in Diagnosis and Targeted Therapy of G719X/L861Q/S768I Mutant Non-small Cell Lung Cancer

TL;DR

This paper reviews advances in diagnosing and treating a rare type of non-small cell lung cancer caused by specific genetic mutations.

Contribution

The paper provides an updated summary of diagnostic methods and treatment outcomes for G719X/L861Q/S768I EGFR-mutant NSCLC.

Findings

Next-generation sequencing and digital PCR are key diagnostic tools for these rare EGFR mutations.

First-generation TKIs show poor efficacy, while second and third-generation TKIs offer better outcomes.

Combination therapies and newer third-generation TKIs show promising treatment potential.

Abstract

肺癌在全球癌症死亡原因中占比最高，对人类健康造成了极大威胁。30%-40%的非小细胞肺癌（non-small cell lung cancer, NSCLC）的发生是由于表皮生长因子受体（epidermal growth factor receptor, EGFR）发生点突变 、外显子插入、外显子缺失导致。除常见的19号外显子缺失突变和21号外显子L858R突变外，18号外显子G719X突变、21号外显子L861Q突变、20号外显子S768I突变是最主要的罕见突变。目前，针对主要罕见突变的诊断方法主要是下一代测序技术（next-generation sequencing, NGS ）、数字聚合酶链式反应（digital polymerase chain reaction, dPCR）、微滴式数字PCR（droplet digital PCR, ddPCR）等。关于G719X/L861Q/S768I突变NSCLC的靶向治疗，第一代EGFR酪氨酸激酶抑制剂（tyrosine kinase inhibitors, TKIs）疗效较差，第二代和第三代EGFR-TKIs疗效相当，新型第三代EGFR-TKIs和联合治疗展现出不错的治疗前景。本文对G719X/L861Q/S768I突变NSCLC诊断及靶向治疗进展进行了归纳，以期为后续临床用药及研究提供参考。

Tissue biopsy in NSCLC with G719X/L861Q/S768I mutations

Liquid biopsy in NSCLC with G719X/L861Q/S768I mutations

Efficacy of the first-generation TKIs in G719X/L861Q/S768I mutated NSCLC

Efficacy of the second-generation TKIs in G719X/L861Q/S768I mutated NSCLC

Efficacy of the third-generation TKIs in G719X/L861Q/S768I mutated NSCLC