Targeting lncRNA-mediated networks to overcome doxorubicin resistance in cancer

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Doxorubicin (DOX) is a cornerstone chemotherapy, but its effectiveness is compromised by acquired drug resistance.
• Long noncoding RNAs (lncRNAs) are increasingly recognized as critical regulators of cancer drug resistance.
• lncRNAs influence multiple cellular processes implicated in DOX resistance, including survival, apoptosis, and metabolism.

Purpose of the Study:

• To review the mechanistic roles of lncRNAs in mediating doxorubicin resistance across various cancer types.
• To explore therapeutic strategies targeting lncRNAs and their downstream pathways for overcoming DOX resistance.
• To propose a translational framework for developing lncRNA-based cancer therapies.

Main Methods:

• Comprehensive literature review integrating cross-cancer evidence on lncRNAs and DOX resistance.
• Analysis of lncRNA regulatory mechanisms, including ceRNA networks and signaling hubs.
• Evaluation of therapeutic opportunities, including direct lncRNA targeting and novel drug delivery systems.

Main Results:

• lncRNAs orchestrate DOX resistance through conserved pathways like PI3K/AKT/mTOR, apoptosis regulation (BCL-2, MCL1), and autophagy.
• lncRNA-mediated resistance involves complex interactions, including competing endogenous RNA (ceRNA) networks.
• Therapeutic interventions targeting lncRNAs, downstream pathways, or utilizing advanced delivery platforms show potential.

Conclusions:

• lncRNAs are pivotal regulators of DOX resistance, offering druggable targets for cancer therapy.
• A translational framework integrating mechanistic insights and clinical strategies is crucial for developing lncRNA-based interventions.
• Targeting lncRNAs holds promise for overcoming chemoresistance and advancing precision oncology.