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Updated: Nov 6, 2025
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
[Comprehensive Genomic Analysis for Small Cell Lung Cancer]
Yuji Shibata1, Hibiki Udagawa, Shingo Matsumoto
1Dept. of Thoracic Oncology, National Cancer Center Hospital East.
Abstract:
Small cell lung cancer(SCLC)is one of the histological types of lung cancer showing the worst prognosis, and is often diagnosed as an inoperable advanced stage disease. Recently, several comprehensive genomic analyses for SCLC have shown that inactivating mutations of tumor suppressor genes such as TP53 and RB1 and MYC family gene amplifications are involved in the development and progression of SCLC. However, actionable gene alterations for targeted therapies have not yet been identified, and there has been no significant advance in the development of targeted therapies for SCLC. In a nationwide lung cancer genome screening project in Japan, LC‒SCRUM‒Japan, a large‒scale genomic analysis was prospectively performed for Japanese SCLC patients, and based on this genomic analysis, a clinical study to evaluate the efficacy of a targeted therapy for PI3K/AKT/mTOR pathway gene‒altered SCLC(EAGLE‒PAT trial)was conducted. In this article, we describe the results of the genomic analysis in LC‒SCRUM‒Japan and the EAGLE‒PAT trial, and also provide the overview of genetic alterations reported in SCLC and the current and future development of targeted therapies for SCLC.
Insights
Genomic analysis of Japanese small cell lung cancer (SCLC) patients identified PI3K/AKT/mTOR pathway alterations. A subsequent clinical trial evaluated targeted therapy efficacy for these SCLC patients.
Area of Science:
- Oncology
- Genomics
- Translational Medicine
Background:
- Small cell lung cancer (SCLC) has a poor prognosis and is often diagnosed at advanced stages.
- Key genetic alterations in SCLC include TP53/RB1 mutations and MYC amplifications, but actionable targets for therapy remain limited.
- Recent genomic analyses have begun to uncover potential therapeutic targets in SCLC.
Purpose of the Study:
- To conduct a large-scale genomic analysis of Japanese SCLC patients (LC-SCRUM-Japan).
- To evaluate the efficacy of targeted therapy for SCLC with PI3K/AKT/mTOR pathway gene alterations (EAGLE-PAT trial).
- To provide an overview of SCLC genetic alterations and targeted therapy development.
Main Methods:
- Prospective, large-scale genomic screening of Japanese SCLC patients.
- Conducting a clinical trial (EAGLE-PAT) to assess targeted therapy in patients with specific gene alterations.
- Reviewing existing literature on SCLC genetic alterations and targeted therapies.
Main Results:
- Identification of PI3K/AKT/mTOR pathway gene alterations in Japanese SCLC patients.
- Evaluation of targeted therapy efficacy in the EAGLE-PAT trial for patients with these alterations.
- Comprehensive overview of SCLC genomic landscape and therapeutic strategies.
Conclusions:
- Genomic profiling is crucial for identifying actionable targets in SCLC.
- Targeted therapies for PI3K/AKT/mTOR pathway alterations show promise in SCLC.
- Further research into SCLC genetics and targeted therapies is warranted.
