Role and potential therapeutic value of histone methyltransferases in drug resistance mechanisms in lung cancer

Sep 21, 2026

A comprehensive review examines how histone methyltransferases (HMTs) contribute to drug resistance in lung cancer and why this epigenetic axis matters clinically. Lung cancer remains highly lethal despite advances in targeted therapy and immunotherapy, with drug resistance limiting effectiveness and worsening prognosis. The review synthesizes evidence linking abnormal HMT expression to mechanisms including metabolic rewiring, cancer-stem-cell gene programs, epithelial-mesenchymal transition, and increased migration, highlighting HMT inhibitors as therapeutic opportunities.

LanguageEnglish

CategoryResearch & Report

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Pages11

Reading Time28 min

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Role and potential therapeutic value of histone methyltransferases in drug resistance mechanisms in lung cancer

Introduction

TYPE Review PUBLISHED 08 March 2024 DOI 10.3389/fonc.2024.1376916 OPEN ACCESS EDITED BY Vivek M. Rangnekar, University of Kentucky, United States REVIEWED BY Mahadev Rao, Manipal University, India Xiaodong Lu, Emory University, United States *CORRESPONDENCE Xiaojing Wang [wangxiaojing8888@163.com](wangxiaojing8888@163.com)[ ](wangxiaojing8888@163.com)Nan Wu [bbmcwunan@163.com](bbmcwunan@163.com) RECEIVED 26 January 2024 ACCEPTED 26 February 2024 PUBLISHED 08 March 2024 CITATION Zhang L, Zhang X, Shi Y, Ni Y, Fei J, Jin Z, Li W, Wang X and Wu N (2024) Role and potential therapeutic value of histone methyltransferases in drug resistance mechanisms in lung cancer. Front. Oncol. 14:1376916 . doi: 10.3389/fonc.2024.1376916 COPYRIGHT © 2024 Zhang, Zhang, Shi, Ni, Fei, Jin, Li, Wang and Wu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Role and potential therapeutic value of histone methyltransferases in drug resistance mechanisms in lung cancer Linxiang Zhang 1,2, Xueying Zhang 1,2, Yan Shi 1,2, Yuhan Ni 1,2, Jiaojiao Fei 1,2, Zhixin Jin 1,2, Wenjuan Li 1,2, Xiaojing Wang 1,2* and Nan Wu 1,2* 1 Key Laboratory of Clinical and Preclinical Research in Respiratory Disease, Molecular Diagnosis Center, The Department of Pulmonary Critical Care Medicine, First Afﬁliated Hospital of Bengbu Medical College, Bengbu, Anhui, China, 2Joint Research Center for Regional Diseases of Institute of Health and Medicine (IHM), The First Afﬁliated Hospital of Bengbu Medical College, Bengbu, China Lung cancer, ranking second globally in both incidence and high mortality among common malignant tumors, presents a signiﬁcant challenge with frequent occurrences of drug resistance despite the continuous emergence of novel therapeutic agents. This exacerbates disease progression, tumor recurrence, and ultimately leads to poor prognosis. Beyond acquired resistance due to genetic mutations, mounting evidence suggests a critical role of epigenetic mechanisms in this process. Numerous studies have indicated abnormal expression of Histone Methyltransferases (HMTs) in lung cancer, with the abnormal activation of certain HMTs closely linked to drug resistance. HMTs mediate drug tolerance in lung cancer through pathways involving alterations in cellular metabolism, upregulation of cancer stem cell-related genes, promotion of epithelial-mesenchymal transition, and enhanced migratory capabilities. The use of HMT inhibitors also opens new avenues for lung cancer treatment, and targeting HMTs may contribute to reversing drug resistance. This comprehensive review delves into the pivotal roles and molecular mechanisms of HMTs in drug resistance in lung cancer, offering a fresh perspective on therapeutic strategies. By thoroughly examining treatment approaches, it provides new insights into understanding drug resistance in lung cancer, supporting personalized treatment, fostering drug development, and propelling lung cancer therapy into novel territories. KEYWORDS lung cancer, histone methyltransferases, epigenetics, drug resistance, cancer therapy Frontiers in Oncology 01 [frontiersin.org](frontiersin.org) 1 Introduction Lung cancer, a prevalent malignant tumor, maintains high incidence and mortality rates globally (1) . Data from 2020 show approximately 2.2 million new lung cancer cases worldwide, accounting for 11.4% of all new malignant tumor cases, ranking second after breast cancer. Lung cancer-related deaths are estimated at 1.8 million, representing 22% of all cancer fatalities, thus becoming the primary cause

FAQs

Why is drug resistance a major problem in lung cancer treatment?

Drug resistance reduces the effectiveness of chemotherapy, targeted therapy, and immunotherapy, hindering precision medicine and contributing to poor outcomes such as progression and recurrence.

What role do histone methyltransferases (HMTs) play in lung cancer drug resistance?

The review describes that abnormal activation of HMTs is linked to drug resistance through epigenetic regulation, including effects on cellular metabolism, cancer stem cell-related gene expression, epithelial-mesenchymal transition, and migratory ability.

How might targeting HMTs help overcome drug resistance?

Using HMT inhibitors is presented as a strategy that opens new avenues for treatment and may help reverse drug resistance by disrupting HMT-driven mechanisms.

Sep 21, 2026

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