P-glycoprotein (P-gp)-driven cancer drug resistance: biological profile, non-coding RNAs, drugs and nanomodulators

• Published in: Drug discovery today 2024-11, Vol.29 (11), p.104161, Article 104161
• Main Authors: Guo, Yang, Ashrafizadeh, Milad, Tambuwala, Murtaza M., Ren, Jun, Orive, Gorka, Yu, Guiping
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - pharmacology; ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism; cancer therapy; drug delivery; drug resistance; Drug Resistance, Neoplasm - drug effects; Humans; Nanoparticles; Neoplasms - drug therapy; Neoplasms - genetics; Neoplasms - metabolism; non-coding RNAs; P-glycoprotein; RNA, Untranslated - metabolism
• ISSN: 1359-6446; 1878-5832; 1878-5832
• DOI: 10.1016/j.drudis.2024.104161

•Cancer therapy has been compromised by the development of drug resistance.•The upregulation of P-glycoprotein (P-gp) can induce chemoresistance.•The overexpression of oncogenic factors mediates P-gp.•Non-coding RNAs can regulate P-gp in cancers.•Nanoparticles can affect P-gp and bypass P-gp for overcoming drug resistance. Drug resistance has compromised the efficacy of chemotherapy. The dysregulation of drug transporters including P-glycoprotein (P-gp) can mediate drug resistance through drug efflux. In this review, we highlight the role of P-gp in cancer drug resistance and the related molecular pathways, including phosphoinositide 3-kinase (PI3K)–Akt, phosphatase and tensin homolog (PTEN) and nuclear factor-κB (NF-κB), along with non-coding RNAs (ncRNAs). Extracellular vesicles secreted by the cells can transport ncRNAs and other proteins to change P-gp activity in cancer drug resistance. P-gp requires ATP to function, and the induction of mitochondrial dysfunction or inhibition of glutamine metabolism can impair P-gp function, thus increasing chemosensitivity. Phytochemicals, small molecules and nanoparticles have been introduced as P-gp inhibitors to increase drug sensitivity in human cancers.