Miles Brittany, Mackey James D
Medical Education, University of Texas Medical Branch, Galveston, USA.
Medical Oncology, Baylor University Medical Center, Dallas, USA.
Cureus. 2021 Feb 21;13(2):e13470. doi: 10.7759/cureus.13470.
Lung cancer is a leading cause of death for both men and women. The treatment of lung cancer has been stifled with pessimism for many years. However, molecularly targeted therapies directed at pathologic epidermal growth factor receptor tyrosine kinases have come to market and, with them, a new tone to an old diagnosis. Treatment of lung cancer is a complex science that requires not only anatomical knowledge of the patient but also an understanding of the patient's overall physiologic condition. When patients are treated appropriately, this drug can transform the natural progression of their disease and improve survival. Interestingly, the clinical solidarity of these first-generation tyrosine kinase inhibitors (TKIs) has become the prelude to a second wave of advances in molecular targeting that we can expect to further improve how we classify and treat lung cancers. Cancers that become resistant to epidermal growth factor receptor (EGFR)-specific TKIs through a secondary mutation are likely to be dependent on the activated kinase for their growth and survival. Therefore, discovering a secondary means of inhibiting EGFR T790M may be therapeutically necessary. This has prompted the preclinical and clinical development of second and third-generation kinase inhibitors. Tumor subtypes are also now being identified, potentially allowing patients to be treated with drugs that most benefit their tumor subtype. We used the TriNetX research platform to analyze the rate of patients being prescribed first, second, and third-generation EGFR TKIs and propose a rationale for the trends seen over time.
肺癌是男性和女性的主要死因。多年来，肺癌的治疗一直笼罩在悲观情绪之中。然而，针对病理性表皮生长因子受体酪氨酸激酶的分子靶向疗法已投放市场，随之而来的是，对这一旧有诊断带来了新的气象。肺癌治疗是一门复杂的科学，不仅需要了解患者的解剖结构，还需要了解患者的整体生理状况。当患者得到恰当治疗时，这种药物可以改变疾病的自然进程并提高生存率。有趣的是，这些第一代酪氨酸激酶抑制剂（TKIs）的临床应用已成为分子靶向治疗第二波进展的前奏，我们有望进一步改进肺癌的分类和治疗方式。通过二次突变对表皮生长因子受体（EGFR）特异性TKIs产生耐药性的癌症，其生长和存活可能依赖于激活的激酶。因此，找到抑制EGFR T790M的第二种方法在治疗上可能是必要的。这促使了第二代和第三代激酶抑制剂的临床前和临床开发。目前肿瘤亚型也正在被识别出来，这有可能让患者使用对其肿瘤亚型最有益的药物进行治疗。我们使用TriNetX研究平台分析了开具第一代、第二代和第三代EGFR TKIs的患者比例，并对随时间推移所观察到的趋势提出了一种解释。
