CDK7 as a New therapeutic target in pancreatic and lung cancer: current evidence and future perspectives.

IF 4.4 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Emilia Di Giovanni, Rita Siino, Antonio Russo, Antonio Galvano, Viviana Bazan, Lorena Incorvaia, Negar Bajalan, Camilla Pecoraro, Daniela Carbone, Patrizia Diana, Elisa Giovannetti, Geng Xu
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Abstract

Introduction: Cyclin-dependent kinase 7 (CDK7) is a key regulator of transcription and the cell cycle, with its dysregulation linked to tumorigenesis and chemoresistance. CDK7 serves as an unfavorable prognostic marker in multiple cancers and is significantly overexpressed in patients with poor prognosis, including those with lung and pancreatic cancer.

Areas covered: This review explores the role of CDK7 in tumorigenesis, focusing on transcriptional regulation, tumor metabolism, and therapy resistance. The development of CDK7 inhibitors has gained attention as a potential strategy to overcome chemoresistance. Notably, cancer cells exhibit sensitivity to CDK7 inhibitors at doses well tolerated by normal cells, supporting their clinical applicability. This review examines key CDK7 inhibitors, including THZ1, LDC4297, and YKL-5-124, in non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), and pancreatic ductal adenocarcinoma (PDAC), highlighting their mechanisms and therapeutic potential. Resistance mechanisms and combination strategies with chemotherapy, targeted therapies, or immunotherapy are also discussed.

Expert opinion: Despite promising preclinical results, challenges remain, including specificity, biomarker identification, and clinical validation. Further research is needed to optimize dosing, address resistance, and translate CDK7 inhibitors into clinical practice. Lastly, ongoing and future clinical trials will be essential to determining their therapeutic potential in PDAC, NSCLC, and SCLC.

CDK7作为胰腺癌和肺癌的新治疗靶点:目前的证据和未来的展望
细胞周期蛋白依赖性激酶7 (Cyclin-dependent kinase 7, CDK7)是转录和细胞周期的关键调控因子,其失调与肿瘤发生和化疗耐药有关。CDK7在多种癌症中作为不利的预后标志物,在包括肺癌和胰腺癌在内的预后不良患者中显著过表达。涵盖领域:本文探讨了CDK7在肿瘤发生中的作用,重点是转录调控、肿瘤代谢和治疗耐药性。CDK7抑制剂的开发作为克服化疗耐药的潜在策略已经引起了人们的关注。值得注意的是,癌细胞在正常细胞耐受的剂量下对CDK7抑制剂表现出敏感性,支持其临床适用性。本文综述了主要的CDK7抑制剂,包括THZ1、LDC4297和YKL-5-124,在非小细胞肺癌(NSCLC)、小细胞肺癌(SCLC)和胰腺导管腺癌(PDAC)中的作用,强调了它们的机制和治疗潜力。耐药机制和联合化疗、靶向治疗或免疫治疗的策略也进行了讨论。专家意见:尽管临床前结果很有希望,但挑战仍然存在,包括特异性、生物标志物鉴定和临床验证。需要进一步的研究来优化剂量,解决耐药问题,并将CDK7抑制剂转化为临床实践。最后,正在进行的和未来的临床试验对于确定它们在PDAC、NSCLC和SCLC中的治疗潜力至关重要。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
8.90
自引率
1.70%
发文量
58
审稿时长
3 months
期刊介绍: The journal evaluates molecules, signalling pathways, receptors and other therapeutic targets and their potential as candidates for drug development. Articles in this journal focus on the molecular level and early preclinical studies. Articles should not include clinical information including specific drugs and clinical trials. The Editors welcome: Reviews covering novel disease targets at the molecular level and information on early preclinical studies and their implications for future drug development. Articles should not include clinical information including specific drugs and clinical trials. Original research papers reporting results of target selection and validation studies and basic mechanism of action studies for investigative and marketed drugs. The audience consists of scientists, managers and decision makers in the pharmaceutical industry, academic researchers working in the field of molecular medicine and others closely involved in R&D.
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