Recent developments in the treatment of small cell lung cancer

Abstract

Small cell lung cancer (SCLC) comprises about 15% of all lung cancers. It is an aggressive disease, with early metastasis and a poor prognosis. Until recently, SCLC treatment remained relatively unchanged, with chemotherapy remaining the cornerstone of treatment. In this overview we will highlight the recent advances in the field of staging, surgery, radiotherapy and systemic treatment. Nevertheless, the prognosis remains dismal and there is a pressing need for new treatment options. We describe the progress that has been made in systemic treatment by repurposing existing drugs and the addition of targeted treatment. In recent years, immunotherapy entered the clinic with high expectations of its role in the treatment of SCLC. Unravelling of the genomic sequence revealed new possible targets that may act as biomarkers in future treatment of patients with SCLC. Hopefully, in the near future, we will be able to identify patients who may benefit from targeted therapy or immunotherapy to improve prognoses.

The 2021 Global Lung Cancer Therapy Landscape

“…2A), most of which are targeted therapies (320 TEs when counted as separate entities for each of the multiple targets or 309 when counted as one entity with multiple targets, accounting for 82% to 85% of the portfolio). 7,8 With 166 TEs, proliferative signaling inhibitors makeup the major fraction of the targeted therapies portfolio. There is continuous activity in the oncogene-driven lung cancer space, as evidenced by the development of proliferative signaling inhibitors for major oncogenic driver targets, such as ALK, BRAF, the EGFR/HER2/ERBB2 family, KRAS, MET, NTRK, RET, and ROS1.…”

Organoids as a Systems Platform for SCLC Brain Metastasis

“…Inactivation of the tumor suppressors TP53 and RB1 is observed in over 99% of SCLC cases, together with extensive chromosomal rearrangements and a high mutational burden that identifies clusters as in other cancer types ( 15 – 19 ). Based on previous work by our laboratory and others, SCLC has been classified into five tumor cell subtypes characterized by eponymous transcription factors ASCL1 (SCLC-A and SCLC-A2), NEUROD1 (SCLC-N), YAP1 (SCLC-Y), or POU2F3 (SCLC-P) ( 8 , 9 , 20 – 23 ).…”

“…Tissue scarcity for primary and metastatic SCLC has been a long-standing obstacle to the molecular characterization of SCLC ( 37 ). Surgery is sometimes offered for very small SCLC with negative lymph nodes, but concomitant chemoradiation is often an alternative treatment plan ( 15 ). A paucity of tissue from patients with relapsed SCLC is even more apparent, as these patients often experience a rapid clinical deterioration ( 37 ).…”

Chemotherapy- and Immune-Related Gene Panel in Prognosis Prediction and Immune Microenvironment of SCLC

“…Recent advances in immunotherapy (e.g., PD-1, PD-L1, and CTLA-4 therapies) have shown promising results for patients with SCLC. Chemotherapy is combined with immunotherapy for SCLC treatment because the disease has a high tumor mutational burden; thus, chemotherapy can stimulate tumoral antigens and increase activation of T cells, thereby enhancing immunogenicity and priming the tumor for the response to immune checkpoint inhibitor treatment ( Mak et al, 2019 ; Hiddinga et al, 2021 ). IMPOWER-133, a phase III trial, demonstrated that immunotherapy (atezolizumab or durvalumab) combined with platinum–etoposide chemotherapy achieved longer progression-free survival (PFS) (6.3 vs. 5.6 months) and patient overall survival (OS) (33.5 vs. 20.4% long-term survivors for control) compared with chemotherapy alone ( Horn et al, 2018 ).…”