Zinc finger proteins and ATP‐binding cassette transporter‐dependent multidrug resistance

Abstract

BackgroundMultidrug resistance (MDR) remains a significant challenge in cancer treatment, leading to poor clinical outcomes. Dysregulation of ATP‐binding cassette (ABC) transporters has been identified as a key contributor to MDR. Zinc finger proteins (ZNPs) are key regulators of transcription and have emerged as potential contributors to cancer drug resistance. Bridging the knowledge gap between ZNPs and MDR is essential to understand a source of heterogeneity in cancer treatment. This review sought to elucidate how different ZNPs modulate the transcriptional regulation of ABC genes, contributing to resistance to cancer therapies.MethodsThe search was conducted using PubMed, Google Scholar, EMBASE and Web of Science.ResultsIn addition to ABC‐blockers, the transcriptional features regulated by ZNP are expected to play a role in reversing ABC‐mediated MDR and predicting the efficacy of anticancer treatments. Among the ZNP‐induced epithelial to mesenchymal transition, SNAIL, SLUG and Zebs have been identified as important factors in promoting MDR through activation of ATM, NFκB and PI3K/Akt pathways, exposing the metabolism to potential ZNP‐MDR interactions. Additionally, nuclear receptors, such as VDR, ER and PXR have been found to modulate certain ABC regulations. Other C2H2‐type zinc fingers, including Kruppel‐like factors, Gli and Sp also have the potential to contribute to MDR.ConclusionBesides reviewing evidence on the effects of ZNP dysregulation on ABC‐related chemoresistance in malignancies, significant markers of ZNP functions are discussed to highlight the clinical implications of gene‐to‐gene and microenvironment‐to‐gene interactions on MDR prospects. Future research on ZNP‐derived biomarkers is crucial for addressing heterogeneity in cancer therapy.

Prospects for the clinical application of exosomal circular RNA in squamous cell carcinoma

“…A significant barrier to the efficacy of these therapies in patients with advanced cancer is the development of resistance to chemotherapy ( 44 ). One of the pivotal mechanisms underpinning this resistance involves ATP-binding cassette B1 (ABCB1), a protein associated with multidrug resistance that is overexpressed in resistant cell lines and facilitates the extracellular expulsion of intracellular chemotherapeutic agents ( 45 , 46 ). Consequently, targeting and inhibiting the expression of ABCB1 is a promising strategy for mitigating drug resistance in tumors ( 47 ).…”

Heat Shock Proteins, a Double-Edged Sword: Significance in Cancer Progression, Chemotherapy Resistance and Novel Therapeutic Perspectives

“…Yet, the ability of Hsp90 to stabilize a transcriptional repressor Snail in response to DNA damage suggests that it can be a mechanism in which Hsp90 contributes to the chemotherapy resistance of cancer. The activation of Snail and the downstream complex signaling network is known to induce several cellular events, including metabolic reprogramming, the EMT and tumor metastasis, which overall promote multidrug resistance [177,178]. Also, the protection and further activation of Akt, a known substrate of Hsp90, in a response to chemotherapy is well established to confer the acquired drug resistance of cancer cells [179]; similarly, the stabilization of the Raf kinase may result in the enhanced activation of the Raf/MEK/ERK pathway, which can govern drug resistance [180].…”