Small cell lung cancer (SCLC) is a malignant disease associated with a particularly high mortality rate. According to a new multicenter study conducted by MedUni Vienna and carried out in collaboration with researchers from the Czech Republic, Hungary, Slovenia, Sweden and the United States, SCLC can be divided into several subgroups in terms of clinical behavior. These subtypes respond differently to chemotherapies and targeted drugs. It also opens up possibilities for personalized treatment for this type of cancer.
SCLC is a particularly aggressive cancer that usually occurs in smokers, showing rapid growth and a high propensity for metastasis. Recent studies suggest that SCLC can be differentiated into specific molecular subtypes. However, due to the significant lack of tumor material and the problem of tumor heterogeneity, this information could not be effectively validated in the clinical setting.
This new research project has now looked at 386 cases from central Europe, one of the largest cohorts of patients treated surgically to date. The results confirmed that the differential expression of ASCL1, NEUROD1 and POU2F3 proteins in tumor tissue defines biologically distinct SCLC subtypes that also have different disease outcomes in surgically resected individuals.
Personalized approach to treatment and follow-up
“Unlike the increasingly personalized approaches seen in non-small cell lung cancer, SCLC is still considered a homogeneous clinical picture and is treated in a standardized way in both hospitals and laboratories,” explains the first. author Zsolt Megyesfalvi from the Translational Thoracic Oncology Laboratory of the Thoracic Surgery Department of the Medical University of Vienna. “We now show that the differential expression of key transcriptional regulators clearly distinguishes five major SCLC subtypes.” The results also show that elevated ASCL1 protein expression is an independent negative prognostic marker, whereas elevated POU2F3 protein expression is associated with more favorable survival outcomes.
Differential Response to Therapies
Researchers also comprehensively described protein expression using mass spectrometry-based proteomics in SCLC cell lines to assess the therapeutic relevance of each SCLC subtype. Study leader Balazs Döme, head of the translational thoracic oncology program at the Medical University of Vienna, commented: “We were able to use experiments with tumor cells to show that the levels of markers defining the under -type also influence response to various targeted therapy and chemotherapeutic agents in vitro.Notably, elevated expression of POU2F3, which is associated with better survival, correlates with susceptibility to standard chemotherapies.In contrast, elevated expression of the YAP1 protein is correlated with a poor response to chemotherapy.In addition, the abundance of subtype-defining proteins was also associated with the efficacy of certain targeted drugs such as CDK, AURK and IGF-1R inhibitors. “
The study is of great clinical relevance, as it sheds light on the diversity of SCLC and helps facilitate the implementation of subtype-specific personalized approaches to treatment and follow-up strategies in this disease.