Thoracic Oncology, Abramson Cancer Center, University of Pennsylvania, 3400 Civic Center Blvd, 2 Perelman Center for Advanced Medicine, Philadelphia, PA 19104, USA.
J Clin Oncol. 2010 Dec 20;28(36):5311-20. doi: 10.1200/JCO.2010.28.8126. Epub 2010 Nov 15.
Until recently, non-small-cell lung cancer (NSCLC) was treated as a single disease despite recognition of its histologic and molecular heterogeneity. Recent clinical trials, however, demonstrate that histology is an important factor for individualizing treatment, based on either safety or efficacy outcomes. For example, the labeling of the licensed agents bevacizumab and pemetrexed is restricted to patients with nonsquamous cell NSCLC. For bevacizumab, this restriction is due to an apparent association between squamous cell histology and severe pulmonary hemorrhage, whereas for pemetrexed, superior treatment effects have been observed in patients with nonsquamous cell histology. Given fewer agents are both active and tolerable in patients with squamous cell carcinoma compared with adenocarcinoma, and the nature of this particular phenotype of NSCLC, new drugs are needed for this histology. In this new histology-based treatment era, questions persist. Can pathology accurately distinguish the histologic subtypes of NSCLC? Can we use cytologic diagnosis? In the future, will molecular profiling of tumors trump histologic analysis? Herein we describe how therapy for NSCLC is evolving on the basis of a better understanding of molecular mechanisms underlying NSCLC histologic heterogeneity and tumorigenesis.
直到最近，非小细胞肺癌（NSCLC）仍被视为一种单一疾病，尽管其组织学和分子异质性已得到认可。然而，最近的临床试验表明，组织学是根据安全性或疗效结果为个体治疗制定方案的重要因素。例如，已获许可的药物贝伐珠单抗和培美曲塞的标签仅限于非鳞状细胞 NSCLC 患者。对于贝伐珠单抗，这种限制是由于鳞状细胞组织学与严重肺出血之间存在明显关联，而对于培美曲塞，在非鳞状细胞组织学患者中观察到了更好的治疗效果。由于与腺癌相比，鳞状细胞癌患者中既有效又耐受的药物较少，并且这种 NSCLC 的特定表型具有特殊性，因此需要针对这种组织学开发新药。在这个基于新组织学的治疗时代，仍存在一些问题。病理能否准确区分 NSCLC 的组织学亚型？我们能否使用细胞学诊断？将来，肿瘤的分子分析是否会超越组织学分析？本文描述了如何在更好地理解 NSCLC 组织学异质性和肿瘤发生的分子机制的基础上，推动 NSCLC 治疗的发展。
