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Abstract：
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.
摘要：
肺癌,在常见恶性肿瘤中，发病率和高死亡率均居全球第二，尽管新的治疗剂不断涌现，但耐药性的频繁发生仍然是一个重大挑战。这会加剧疾病进展，肿瘤复发,最终导致预后不良。除了遗传突变导致的获得性抗性，越来越多的证据表明，表观遗传机制在这一过程中起着至关重要的作用。大量研究表明组蛋白甲基转移酶（HMTs）在肺癌中表达异常，某些HMTs的异常激活与耐药性密切相关。HMTs通过涉及细胞代谢改变的途径介导肺癌的药物耐受性，肿瘤干细胞相关基因的上调，促进上皮-间质转化，增强迁移能力。HMT抑制剂的使用也为肺癌治疗开辟了新的途径，靶向HMT可能有助于逆转耐药性。本文综述了HMTs在肺癌耐药中的关键作用和分子机制。为治疗策略提供了新的视角。通过彻底检查治疗方法，它为了解肺癌的耐药性提供了新的见解，支持个性化治疗，促进药物开发，并将肺癌治疗推向新的领域。
