# Advancements in extensive-stage small cell lung cancer therapy: from molecular profiling to the advent of precision oncology

**Authors:** Chen Yang, Yanchi Shao, Yu Zhang, Huan Zhang, Yanbin Zhao

PMC · DOI: 10.3389/fimmu.2025.1674449 · Frontiers in Immunology · 2025-11-05

## TL;DR

This review discusses recent progress in treating advanced small cell lung cancer, focusing on new therapies and strategies to improve patient outcomes.

## Contribution

The paper synthesizes recent multimodal and precision oncology approaches to enhance treatment efficacy in extensive-stage SCLC.

## Key findings

- Immune checkpoint inhibitors have improved survival in extensive-stage SCLC but with limited clinical benefits.
- Multimodal regimens combining chemoimmunotherapy with targeted therapy or radiotherapy are being explored to optimize first-line treatment.
- Emerging therapies like DLL3-targeted agents and CAR-T show clinical promise for SCLC.

## Abstract

Small cell lung cancer (SCLC) is challenging to manage due to its high malignancy and early metastatic spread. Although initial chemoradiotherapy responses are common, resistance rapidly develops, and long-term efficacy remains limited. Immune checkpoint inhibitors (ICIs) overcome previous survival barriers, extending overall survival (OS) and progression-free survival (PFS) in extensive-stage SCLC. Nevertheless, absolute clinical benefits remain modest. To address efficacy limitations, current research focuses on optimizing first-line strategies by exploring multimodal regimens (e.g., adding targeted therapy or radiotherapy to chemoimmunotherapy) and advancing molecular subtyping for precision oncology. Furthermore, emerging therapies such as DLL3-targeted agents, bispecific antibodies (bsAbs), antibody-drug conjugates (ADCs), and chimeric antigen receptor T-cell (CAR-T) therapy continue to demonstrate clinical progress. This review synthesizes advances in SCLC management, focusing on mechanisms and clinical applications of multimodal strategies and novel therapies. It provides guidance for clinical decisions, research directions, and survival improvement.

## Linked entities

- **Proteins:** DLL3 (delta like canonical Notch ligand 3)
- **Diseases:** small cell lung cancer (MONDO:0008433), SCLC (MONDO:0008433)

## Full-text entities

- **Genes:** DLL3 (delta like canonical Notch ligand 3) [NCBI Gene 10683] {aka SCDO1}
- **Diseases:** malignancy (MESH:D009369), SCLC (MESH:D055752)

## Full text

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## Figures

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## References

77 references — full list in the complete paper: https://tomesphere.com/paper/PMC12626867/full.md

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Source: https://tomesphere.com/paper/PMC12626867