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

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.

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.

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.