Advances in molecular pathology and therapy of non-small cell lung cancer

Abstract Over the past two decades, non-small cell lung cancer (NSCLC) has witnessed encouraging advancements in basic and clinical research. However, substantial unmet needs remain for patients worldwide, as drug resistance persists as an inevitable reality. Meanwhile, the journey towards amplifyin...

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Main Authors: Qing Huang, Yuanxiang Li, Yingdan Huang, Jingyi Wu, Wendai Bao, Chang Xue, Xiaoyu Li, Shuang Dong, Zhiqiang Dong, Sheng Hu
Format: Article
Language:English
Published: Nature Publishing Group 2025-06-01
Series:Signal Transduction and Targeted Therapy
Online Access:https://doi.org/10.1038/s41392-025-02243-6
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author Qing Huang
Yuanxiang Li
Yingdan Huang
Jingyi Wu
Wendai Bao
Chang Xue
Xiaoyu Li
Shuang Dong
Zhiqiang Dong
Sheng Hu
author_facet Qing Huang
Yuanxiang Li
Yingdan Huang
Jingyi Wu
Wendai Bao
Chang Xue
Xiaoyu Li
Shuang Dong
Zhiqiang Dong
Sheng Hu
author_sort Qing Huang
collection DOAJ
description Abstract Over the past two decades, non-small cell lung cancer (NSCLC) has witnessed encouraging advancements in basic and clinical research. However, substantial unmet needs remain for patients worldwide, as drug resistance persists as an inevitable reality. Meanwhile, the journey towards amplifying the breadth and depth of the therapeutic effect requires comprehending and integrating diverse and profound progress. In this review, therefore, we aim to comprehensively present such progress that spans the various aspects of molecular pathology, encompassing elucidations of metastatic mechanisms, identification of therapeutic targets, and dissection of spatial omics. Additionally, we also highlight the numerous small molecule and antibody drugs, encompassing their application alone or in combination, across later-line, frontline, neoadjuvant or adjuvant settings. Then, we elaborate on drug resistance mechanisms, mainly involving targeted therapies and immunotherapies, revealed by our proposed theoretical models to clarify interactions between cancer cells and a variety of non-malignant cells, as well as almost all the biological regulatory pathways. Finally, we outline mechanistic perspectives to pursue innovative treatments of NSCLC, through leveraging artificial intelligence to incorporate the latest insights into the design of finely-tuned, biomarker-driven combination strategies. This review not only provides an overview of the various strategies of how to reshape available armamentarium, but also illustrates an example of clinical translation of how to develop novel targeted drugs, to revolutionize therapeutic landscape for NSCLC.
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spelling doaj-art-eb3062e152aa4f14971c67d8b1e4b8162025-08-20T02:06:36ZengNature Publishing GroupSignal Transduction and Targeted Therapy2059-36352025-06-0110117210.1038/s41392-025-02243-6Advances in molecular pathology and therapy of non-small cell lung cancerQing Huang0Yuanxiang Li1Yingdan Huang2Jingyi Wu3Wendai Bao4Chang Xue5Xiaoyu Li6Shuang Dong7Zhiqiang Dong8Sheng Hu9Department of Medical Oncology, Huazhong University of Science and Technology, Tongji Medical College, Hubei Cancer HospitalDepartment of Medical Oncology, Huazhong University of Science and Technology, Tongji Medical College, Hubei Cancer HospitalDepartment of Medical Oncology, Huazhong University of Science and Technology, Tongji Medical College, Hubei Cancer HospitalDepartment of Medical Oncology, Huazhong University of Science and Technology, Tongji Medical College, Hubei Cancer HospitalCenter for Neurological Disease Research, Taihe Hospital, Hubei University of MedicineDepartment of Medical Oncology, Huazhong University of Science and Technology, Tongji Medical College, Hubei Cancer HospitalDepartment of Medical Oncology, Huazhong University of Science and Technology, Tongji Medical College, Hubei Cancer HospitalDepartment of Medical Oncology, Huazhong University of Science and Technology, Tongji Medical College, Hubei Cancer HospitalDepartment of Medical Oncology, Huazhong University of Science and Technology, Tongji Medical College, Hubei Cancer HospitalDepartment of Medical Oncology, Huazhong University of Science and Technology, Tongji Medical College, Hubei Cancer HospitalAbstract Over the past two decades, non-small cell lung cancer (NSCLC) has witnessed encouraging advancements in basic and clinical research. However, substantial unmet needs remain for patients worldwide, as drug resistance persists as an inevitable reality. Meanwhile, the journey towards amplifying the breadth and depth of the therapeutic effect requires comprehending and integrating diverse and profound progress. In this review, therefore, we aim to comprehensively present such progress that spans the various aspects of molecular pathology, encompassing elucidations of metastatic mechanisms, identification of therapeutic targets, and dissection of spatial omics. Additionally, we also highlight the numerous small molecule and antibody drugs, encompassing their application alone or in combination, across later-line, frontline, neoadjuvant or adjuvant settings. Then, we elaborate on drug resistance mechanisms, mainly involving targeted therapies and immunotherapies, revealed by our proposed theoretical models to clarify interactions between cancer cells and a variety of non-malignant cells, as well as almost all the biological regulatory pathways. Finally, we outline mechanistic perspectives to pursue innovative treatments of NSCLC, through leveraging artificial intelligence to incorporate the latest insights into the design of finely-tuned, biomarker-driven combination strategies. This review not only provides an overview of the various strategies of how to reshape available armamentarium, but also illustrates an example of clinical translation of how to develop novel targeted drugs, to revolutionize therapeutic landscape for NSCLC.https://doi.org/10.1038/s41392-025-02243-6
spellingShingle Qing Huang
Yuanxiang Li
Yingdan Huang
Jingyi Wu
Wendai Bao
Chang Xue
Xiaoyu Li
Shuang Dong
Zhiqiang Dong
Sheng Hu
Advances in molecular pathology and therapy of non-small cell lung cancer
Signal Transduction and Targeted Therapy
title Advances in molecular pathology and therapy of non-small cell lung cancer
title_full Advances in molecular pathology and therapy of non-small cell lung cancer
title_fullStr Advances in molecular pathology and therapy of non-small cell lung cancer
title_full_unstemmed Advances in molecular pathology and therapy of non-small cell lung cancer
title_short Advances in molecular pathology and therapy of non-small cell lung cancer
title_sort advances in molecular pathology and therapy of non small cell lung cancer
url https://doi.org/10.1038/s41392-025-02243-6
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