What Is On the Horizon for the Diagnosis and Treatment of SCLC and Large Cell Neuroendocrine Cancer?

SCLC is a high-grade neuroendocrine malignancy associated with poor prognosis, comprising 15% of lung cancer cases globally. Advances in genetic profiling have revealed that SCLC is a molecularly heterogeneous disease, categorized into subtypes such as SCLC-A, SCLC-N, SCLC-P, and SCLC-I, on the basi...

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Main Authors: Sun Min Lim, MD, PhD, Joo Sung Gabriel Shim, MD, Hyo Sup Shim, MD, PhD, Junko Tanizaki, MD, PhD, Jorn Nutzinger, MD, Byoung Chul Cho, MD, PhD, Ross A. Soo, MBBS, PhD
Format: Article
Language:English
Published: Elsevier 2025-09-01
Series:JTO Clinical and Research Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2666364325000888
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author Sun Min Lim, MD, PhD
Joo Sung Gabriel Shim, MD
Hyo Sup Shim, MD, PhD
Junko Tanizaki, MD, PhD
Jorn Nutzinger, MD
Byoung Chul Cho, MD, PhD
Ross A. Soo, MBBS, PhD
author_facet Sun Min Lim, MD, PhD
Joo Sung Gabriel Shim, MD
Hyo Sup Shim, MD, PhD
Junko Tanizaki, MD, PhD
Jorn Nutzinger, MD
Byoung Chul Cho, MD, PhD
Ross A. Soo, MBBS, PhD
author_sort Sun Min Lim, MD, PhD
collection DOAJ
description SCLC is a high-grade neuroendocrine malignancy associated with poor prognosis, comprising 15% of lung cancer cases globally. Advances in genetic profiling have revealed that SCLC is a molecularly heterogeneous disease, categorized into subtypes such as SCLC-A, SCLC-N, SCLC-P, and SCLC-I, on the basis of their neuroendocrine and immune-related characteristics. This heterogeneity underscores the need for tailored therapeutic strategies.Large cell neuroendocrine carcinoma (LCNEC) shares histologic and molecular similarities with SCLC but remains a distinct entity. LCNEC is categorized into two major subtypes: Type I, characterized by STK11 and KEAP1 mutations and a neuroendocrine phenotype, and Type II, defined by TP53 and RB1 alterations with higher proliferative indices. LCNEC's rarity and molecular diversity present challenges for standardized treatment, further highlighting the need for comparative research with SCLC.In this review, we highlight the genetic and clinicopathologic features of SCLC and LCNEC. Furthermore, we discuss emerging therapeutics and future directions in the treatment of SCLC and LCNEC.
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spelling doaj-art-94be2d2c92ae4137a81e6aa6cd32e5522025-08-20T03:40:37ZengElsevierJTO Clinical and Research Reports2666-36432025-09-016910087110.1016/j.jtocrr.2025.100871What Is On the Horizon for the Diagnosis and Treatment of SCLC and Large Cell Neuroendocrine Cancer?Sun Min Lim, MD, PhD0Joo Sung Gabriel Shim, MD1Hyo Sup Shim, MD, PhD2Junko Tanizaki, MD, PhD3Jorn Nutzinger, MD4Byoung Chul Cho, MD, PhD5Ross A. Soo, MBBS, PhD6Division of Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of KoreaDepartment of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of KoreaDepartment of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of KoreaDepartment of Medical Oncology, Kindai University, Faculty of Medicine, Osaka, JapanDepartment of Haematology-Oncology, National University Cancer Institute, SingaporeDivision of Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of KoreaDepartment of Haematology-Oncology, National University Cancer Institute, Singapore; Corresponding author. Address for correspondence: Ross A. Soo, MBBS, PhD, Department of Haematology–Oncology, National University Cancer Institute, Level 7 NUHS Tower Block, 1E Kent Ridge Road, 119228 Singapore.SCLC is a high-grade neuroendocrine malignancy associated with poor prognosis, comprising 15% of lung cancer cases globally. Advances in genetic profiling have revealed that SCLC is a molecularly heterogeneous disease, categorized into subtypes such as SCLC-A, SCLC-N, SCLC-P, and SCLC-I, on the basis of their neuroendocrine and immune-related characteristics. This heterogeneity underscores the need for tailored therapeutic strategies.Large cell neuroendocrine carcinoma (LCNEC) shares histologic and molecular similarities with SCLC but remains a distinct entity. LCNEC is categorized into two major subtypes: Type I, characterized by STK11 and KEAP1 mutations and a neuroendocrine phenotype, and Type II, defined by TP53 and RB1 alterations with higher proliferative indices. LCNEC's rarity and molecular diversity present challenges for standardized treatment, further highlighting the need for comparative research with SCLC.In this review, we highlight the genetic and clinicopathologic features of SCLC and LCNEC. Furthermore, we discuss emerging therapeutics and future directions in the treatment of SCLC and LCNEC.http://www.sciencedirect.com/science/article/pii/S2666364325000888Small cell lung cancerLarge cell neuroendocrine carcinomaDiagnosticsNovel therapies
spellingShingle Sun Min Lim, MD, PhD
Joo Sung Gabriel Shim, MD
Hyo Sup Shim, MD, PhD
Junko Tanizaki, MD, PhD
Jorn Nutzinger, MD
Byoung Chul Cho, MD, PhD
Ross A. Soo, MBBS, PhD
What Is On the Horizon for the Diagnosis and Treatment of SCLC and Large Cell Neuroendocrine Cancer?
JTO Clinical and Research Reports
Small cell lung cancer
Large cell neuroendocrine carcinoma
Diagnostics
Novel therapies
title What Is On the Horizon for the Diagnosis and Treatment of SCLC and Large Cell Neuroendocrine Cancer?
title_full What Is On the Horizon for the Diagnosis and Treatment of SCLC and Large Cell Neuroendocrine Cancer?
title_fullStr What Is On the Horizon for the Diagnosis and Treatment of SCLC and Large Cell Neuroendocrine Cancer?
title_full_unstemmed What Is On the Horizon for the Diagnosis and Treatment of SCLC and Large Cell Neuroendocrine Cancer?
title_short What Is On the Horizon for the Diagnosis and Treatment of SCLC and Large Cell Neuroendocrine Cancer?
title_sort what is on the horizon for the diagnosis and treatment of sclc and large cell neuroendocrine cancer
topic Small cell lung cancer
Large cell neuroendocrine carcinoma
Diagnostics
Novel therapies
url http://www.sciencedirect.com/science/article/pii/S2666364325000888
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