Background:Small cell lung cancer (SCLC) is a lethal form of lung cancer with few treatment options and a high rate of relapse. While SCLC is initially sensitive to first-line DNA-damaging chemo- and radiotherapy, relapse disease is almost universally therapy-resistant. As a result, there has been interest in understanding the mechanisms of therapeutic resistance in this disease.Conclusions:Progress has been made in elucidating these mechanisms, particularly as they relate to the DNA damage response and SCLC differentiation and transformation, leading to many clinical trials investigating new therapies and combinations. Yet there remain many gaps in our understanding, such as the effect of epigenetics or the tumor microenvironment on treatment response, and no single mechanism has been found to be ubiquitous, suggesting a significant heterogeneity in the mechanisms of acquired resistance. Nevertheless, the advancement of techniques in the laboratory and the clinic will improve our ability to study this disease, especially in patient populations, and identify methods to surmount therapeutic resistance.
背景：小细胞肺癌（SCLC）是一种致死率高的肺癌类型，治疗选择有限且复发率高。尽管小细胞肺癌初期对一线DNA损伤性化疗和放疗敏感，但复发疾病几乎普遍存在治疗抵抗性。因此，探索该疾病治疗抵抗机制的研究备受关注。 结论：在阐明这些机制方面已取得进展，特别是与DNA损伤反应及小细胞肺癌分化与转化相关的机制，这推动了许多针对新疗法及联合疗法的临床试验。然而，我们的理解仍存在诸多空白，例如表观遗传学或肿瘤微环境对治疗反应的影响，且尚未发现普遍存在的单一抵抗机制，这表明获得性耐药机制具有显著的异质性。尽管如此，实验室与临床技术的进步将提升我们研究该疾病的能力（尤其在患者群体中），并有助于找到克服治疗抵抗的方法。
Strategies to Target Chemoradiotherapy Resistance in Small Cell Lung Cancer
肿瘤(癌症)患者之家