Worldwide, lung cancer is one of the most common cancers, with non-small cell lung cancer (NSCLC) including up to 80–85% of all lung cancer diagnoses. The landscape of NSCLC is characterized by a heterogeneous spectrum of gene alterations, with tyrosine kinase inhibitors (TKIs) and targeted treatments that significantly improve survival outcomes for patients with oncogene-addicted NSCLC, offering superior efficacy, and often favorable safety and tolerability profiles compared to chemotherapy-based treatments. However, the complexity of NSCLC extends to co-occurring genomic alterations or amplifications in tumor suppressors and other oncogenes, such asTP53,STK11,KEAP1,PIK3CA,RB1, and others, that significantly influence disease progression, therapeutic resistance, and clinical outcomes. These co-mutations often contribute to the development of primary and acquired resistance to targeted therapies, complicating decision-making strategies. This review provides a timely and comprehensive synthesis of current insights into co-mutations in NSCLC, with a particular focus on their clinical implications, and offers a novel perspective by integrating recent molecular insights with therapeutic challenges, addressing existing knowledge gaps through a more integrative and clinically oriented analysis of co-mutations. Advances in next-generation sequencing (NGS) and molecular profiling have enabled the identification of these co-alterations, paving the way for more personalized therapeutic approaches. However, challenges remain in interpreting the functional interplay of co-mutations and translating these insights into effective clinical interventions. This review also highlights the significance of co-mutations in shaping NSCLC biology, and discusses their impact on current therapeutic paradigms, emphasizing the need for integrative biomarker-driven approaches to improve outcomes in NSCLC.
在全球范围内，肺癌是最常见的恶性肿瘤之一，其中非小细胞肺癌（NSCLC）约占所有肺癌诊断的80%至85%。NSCLC的疾病特征表现为基因改变的异质性谱系，酪氨酸激酶抑制剂（TKIs）及其他靶向治疗显著改善了致癌基因依赖型NSCLC患者的生存结局，与化疗相比通常具有更优的疗效及良好的安全性和耐受性。然而，NSCLC的复杂性还体现在肿瘤抑制基因及其他致癌基因（如TP53、STK11、KEAP1、PIK3CA、RB1等）中并存基因组改变或扩增，这些共突变显著影响疾病进展、治疗耐药及临床结局。这些共突变常导致靶向治疗的原发性和获得性耐药，使临床决策策略复杂化。本综述及时全面地整合了当前对NSCLC共突变的认识，特别关注其临床意义，并通过整合最新分子学见解与治疗挑战，以更具整合性和临床导向的共突变分析填补现有知识空白，提供了新颖的视角。新一代测序（NGS）和分子谱分析技术的进步使得这些共改变得以识别，为更个性化的治疗策略铺平了道路。然而，在阐释共突变的功能性相互作用及将这些发现转化为有效临床干预方面仍存在挑战。本综述还强调了共突变在塑造NSCLC生物学特性中的重要意义，探讨了其对当前治疗模式的影响，并强调需要采用整合性生物标志物驱动策略以改善NSCLC患者的临床结局。
Co-Occurring Genomic Alterations in NSCLC: Making Order into a Crowded List
肿瘤(癌症)患者之家