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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引用次数: 0
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.
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.