Emerging Strategies for the Treatment of Small Cell Lung Cancer A Review

被引:83
|
作者
Petty, W. Jeffrey [1 ]
Paz-Ares, Luis [2 ,3 ,4 ]
机构
[1] Wake Forest Univ, Wake Forest Sch Med, Dept Internal Med, Sect Hematol & Oncol,Comprehens Canc Ctr, Winston Salem, NC USA
[2] Hosp Univ 12 Octubre, Madrid, Spain
[3] H120 CNIO Lung Canc Unit, Madrid, Spain
[4] Univ Complutense Madrid, Ctr Invest Biomed Red Canc, Madrid, Spain
关键词
PROPHYLACTIC CRANIAL IRRADIATION; PLACEBO PLUS ETOPOSIDE; PHASE-III TRIAL; OPEN-LABEL; ES-SCLC; THORACIC RADIOTHERAPY; 1ST-LINE TREATMENT; 2ND-LINE TREATMENT; STAGE; CHEMOTHERAPY;
D O I
10.1001/jamaoncol.2022.5631
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Importance Small cell lung cancer (SCLC) is an aggressive disease that is characterized by rapid growth and the early development of metastases. Patients typically respond to initial chemotherapy but quickly experience relapse, resulting in a poor long-term outcome. Therapeutic innovations that substantially improve survival have historically been limited, and reliable, predictive biomarkers are lacking.Observations This review examines the biologic characteristics of SCLC, the current treatment landscape, and ongoing efforts to identify novel therapeutic targets. Ongoing research has advanced the understanding of molecular categories and the immunologic microenvironment of SCLC, which in turn has helped improve disease classification and staging. Recently, immunotherapy-based regimens have become available for the management of SCLC, with 2 programmed cell death 1 ligand 1 inhibitors approved in combination with chemotherapy for first-line treatment of extensive-stage disease. For second-line treatment, a novel alkylating agent, lurbinectedin, which inhibits oncogenic transcription, has been approved for use in patients with metastatic SCLC. Furthermore, a wide variety of therapies and innovative combination regimens are being continuously evaluated. Potential therapeutic strategies, including aurora kinase A inhibitors, polyadenosine diphosphate-ribose polymerase inhibitors, ataxia telangiectasia and Rad3-related inhibitors, cyclin-dependent kinase 7 inhibitors, delta-like protein 3 agents, antiganglioside agents, CD47 inhibitors, and lysine-specific histone demethylase 1a inhibitors, are also being examined.Conclusions and Relevance Therapeutic optimization of SCLC remains a challenge, but recent trial results and drug approvals are encouraging. Advances in research have revealed critical information regarding biologic characteristics of the disease, which may lead to the identification of vulnerabilities and the development of new therapies. Further research focused on identifying biomarkers and evaluating innovative therapies will be paramount to improving treatment outcomes for patients with SCLC.
引用
收藏
页码:419 / 429
页数:11
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