Wei Yuxuan, Wang Lei, Jin Zheng, Jia Qingzhu, Brcic Luka, Akaba Tomohiro, Chu Qian
Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
Institute of Life Sciences, Chongqing Medical University, Chongqing, China.
Transl Lung Cancer Res. 2024 Mar 29;13(3):635-653. doi: 10.21037/tlcr-24-127. Epub 2024 Mar 27.
Pulmonary sarcomatoid carcinoma (PSC) is a subset of non-small cell lung cancer (NSCLC) with highly malignant, aggressive, and heterogeneous features. Patients with this disease account for approximately 0.1-0.4% of lung cancer cases. The absence of comprehensive summaries on the basic biology and clinical treatments for PSC means there is limited systematic awareness and understanding of this rare disease. This paper provides an overview of the biological characteristics of PSC and systematically summarizes various treatment strategies available for patients with this disease.
For this narrative review, we have searched literature related to the basic biology and clinical treatment approaches of PSC by searching the PubMed database for articles published from July 16, 1990 to August 29, 2023. The following keywords were used: "pulmonary sarcomatoid carcinoma", "genetic mutations", "immune microenvironment", "hypoxia", "angiogenesis", "overall survival", "surgery", "radiotherapy", "chemotherapy", and "immune checkpoint inhibitors".
Classical PSC comprises epithelial and sarcomatoid components, with most studies suggesting a common origin. PSC exhibits a higher tumor mutational burden (TMB) and mutation frequency than other types of NSCLC. The tumor microenvironment (TME) of PSC is characterized by hypoxia, hypermetabolism, elevated programmed cell death protein 1/programmed cell death-ligand 1 expression, and high immune cell infiltration. Treatment strategies for advanced PSC are mainly based on traditional NSCLC treatments, but PSC exhibits resistance to chemotherapy and radiotherapy. The advancement of genome sequencing has introduced targeted therapies as an option for mutation-positive PSC cases. Moreover, due to the characteristics of the immune microenvironment of PSC, many patients positively respond to immunotherapy, demonstrating its potential for the management of PSC.
Although several studies have examined and assessed the TME of PSC, these are limited in quantity and quality, presenting challenges for research into the clinical treatment strategies for PSC. With the emergence of new technologies and the advancement of clinical research, for example, savolitinib's clinical study for exon 14 skipping mutations positive PSC patients have shown promising outcomes, more in-depth studies on PSC are eagerly anticipated.
肺肉瘤样癌（PSC）是非小细胞肺癌（NSCLC）的一个亚型，具有高度恶性、侵袭性和异质性特征。该疾病患者约占肺癌病例的0.1 - 0.4%。目前缺乏关于PSC基础生物学和临床治疗的全面综述，这意味着对这种罕见疾病的系统认识和理解有限。本文概述了PSC的生物学特征，并系统总结了针对该疾病患者的各种治疗策略。
在本叙述性综述中，我们通过检索PubMed数据库中1990年7月16日至2023年8月29日发表的文章，搜索了与PSC基础生物学和临床治疗方法相关的文献。使用了以下关键词：“肺肉瘤样癌”、“基因突变”、“免疫微环境”、“缺氧”、“血管生成”、“总生存期”、“手术”、“放疗”、“化疗”和“免疫检查点抑制剂”。
经典的PSC由上皮和肉瘤样成分组成，大多数研究表明其起源相同。PSC比其他类型的NSCLC表现出更高的肿瘤突变负荷（TMB）和突变频率。PSC的肿瘤微环境（TME）具有缺氧、高代谢、程序性细胞死亡蛋白1/程序性细胞死亡配体1表达升高以及免疫细胞浸润高的特点。晚期PSC的治疗策略主要基于传统的NSCLC治疗方法，但PSC对化疗和放疗具有抗性。基因组测序的进展引入了靶向治疗作为突变阳性PSC病例的一种选择。此外，由于PSC免疫微环境的特点，许多患者对免疫治疗有阳性反应，显示出其在PSC治疗中的潜力。
尽管有多项研究对PSC的TME进行了检查和评估，但这些研究在数量和质量上都有限，这给PSC临床治疗策略的研究带来了挑战。随着新技术的出现和临床研究的进展，例如，赛沃替尼针对外显子14跳跃突变阳性PSC患者的临床研究已显示出有前景的结果，人们急切期待对PSC进行更深入的研究。
