Zhang Chenyue, Wang Haiyong
Department of Integrated Therapy, Fudan University Shanghai Cancer Center, Shanghai Medical College, Shanghai, China.
Department of Internal Medicine-Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.
Biochim Biophys Acta Rev Cancer. 2022 Sep;1877(5):188798. doi: 10.1016/j.bbcan.2022.188798. Epub 2022 Sep 10.
Small cell lung cancer (SCLC) is a deadly disease with poor prognosis. Fast growing speed, inclination to metastasis, enrichment in cancer stem cells altogether constitute its aggressive nature. In stark contrast to non-small cell lung cancer (NSCLC) that strides vigorously on the road to precision oncology, SCLC has been on the embryonic path to achieve effective personalized treatments. The survival of patients with SCLC have not been improved greatly, which could be possibly due to our inadequate understanding of genetic alterations of SCLC. Recently, encouraging effects have been observed in patients with SCLC undergoing immunotherapy. However, exciting results have only been observed in a small fraction of patients with SCLC, warranting biomarkers predictive of responses as well as novel therapeutic strategies. In addition, SCLC has previously been viewed to be homogeneous. However, perspectives have been changed thanks to the advances in sequencing techniques and platforms, which unfolds the complex heterogeneity of SCLC both genetically and non-genetically, rendering the treatment of SCLC a further step forward into the precision era. To outline the road of SCLC towards precision oncology, we summarize the progresses and achievements made in precision treatment in SCLC in genomic, transcriptomic, epigenetic, proteomic and metabolic dimensions. Moreover, we conclude relevant therapeutic vulnerabilities in SCLC. Clinically tested drugs and clinical trials have also been demonstrated. Ultimately, we look into the opportunities and challenges ahead to advance the individualized treatment in pursuit of improved survival for patients with SCLC.
小细胞肺癌(SCLC)是一种预后较差的致命性疾病。其生长速度快、易于转移、富含癌症干细胞,这些共同构成了它的侵袭性。与在精准肿瘤学道路上大步迈进的非小细胞肺癌(NSCLC)形成鲜明对比的是,SCLC仍处于实现有效个性化治疗的起步阶段。SCLC患者的生存率并未得到显著提高,这可能是由于我们对SCLC基因改变的了解不足。最近,接受免疫治疗的SCLC患者已观察到令人鼓舞的疗效。然而,仅在一小部分SCLC患者中观察到了令人兴奋的结果,因此需要预测反应的生物标志物以及新的治疗策略。此外,SCLC此前被认为具有同质性。然而,测序技术和平台的进步改变了这一观点,这些技术揭示了SCLC在基因和非基因方面的复杂异质性,使SCLC的治疗进一步迈向精准时代。为了勾勒出SCLC走向精准肿瘤学的道路,我们总结了SCLC在基因组、转录组、表观遗传、蛋白质组和代谢层面精准治疗方面取得的进展和成就。此外,我们总结了SCLC相关的治疗弱点。还展示了经过临床测试的药物和临床试验。最终,我们展望了未来推进个体化治疗以提高SCLC患者生存率所面临的机遇和挑战。