2026-04-13T07:38:10Zhttps://recercat.cat/oai/request
oai:recercat.cat:10256/207862024-06-18T12:41:37Zcom_2072_452955com_2072_2054col_2072_453079
RECERCAT author Verdura, Sara author Cuyàs, Elisabet author Ruiz-Torres, Verónica author Micol, Vicente author Joven, Jorge author Bosch Barrera, Joaquim author Menéndez Menéndez, Javier Abel 2024-06-18T12:41:37Z 2024-06-18T12:41:37Z 2021-06-11 http://hdl.handle.net/10256/20786 The flavonolignan silibinin, the major bioactive component of the silymarin extract of Silybum marianum (milk thistle) seeds, is gaining traction as a novel anti-cancer therapeutic. Here, we review the historical developments that have laid the groundwork for the evaluation of silibinin as a chemopreventive and therapeutic agent in human lung cancer, including translational insights into its mechanism of action to control the aggressive behavior of lung carcinoma subtypes prone to metastasis. First, we summarize the evidence from chemically induced primary lung tumors supporting a role for silibinin in lung cancer prevention. Second, we reassess the preclinical and clinical evidence on the effectiveness of silibinin against drug resistance and brain metastasis traits of lung carcinomas. Third, we revisit the transcription factor STAT3 as a central tumor-cell intrinsic and microenvironmental target of silibinin in primary lung tumors and brain metastasis. Finally, by unraveling the selective vulnerability of silibinin-treated tumor cells to drugs using CRISPR-based chemosensitivity screenings (e.g., the hexosamine biosynthesis pathway inhibitor azaserine), we illustrate how the therapeutic use of silibinin against targetable weaknesses might be capitalized in specific lung cancer subtypes (e.g., KRAS/STK11 co-mutant tumors). Forthcoming studies should take up the challenge of developing silibinin and/or next-generation silibinin derivatives as novel lung cancer-preventive and therapeutic biomolecules Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess Metàstasi Metastasis Pulmons -- Càncer -- Tractament Lungs -- Cancer -- Treatment Medicaments antineoplàstics Antineoplastic agents Lung Cancer Management with Silibinin: A Historical and Translational Perspective info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion peer-reviewed