Extracellular Vesicles and Cancer Multidrug Resistance: Undesirable Intercellular Messengers?

Area of Science:

• Oncology
• Cell Biology
• Molecular Medicine

Background:

• Cancer multidrug resistance (MDR) significantly limits therapeutic efficacy and survival rates.
• Overexpression of ATP-binding cassette (ABC) transporters is a primary driver of MDR.
• Extracellular vesicles (EVs) are key mediators of intercellular communication, transferring molecular cargo and influencing recipient cell phenotypes.

Purpose of the Study:

• To review existing scientific evidence on the regulation of ABC transporters via EV-mediated intercellular communication.
• To explore the role of EVs in the transfer of MDR between cancer cells.
• To discuss potential therapeutic strategies targeting EV-mediated MDR.

Main Methods:

• Literature review of studies investigating EV-mediated communication in cancer multidrug resistance.
• Analysis of mechanisms by which EVs transfer ABC transporters, coding mRNA, regulatory proteins, and noncoding RNAs.
• Examination of evidence for MDR transfer and drug-sensitive phenotype transfer via EVs.

Main Results:

• EVs can transfer MDR by shuttling ABC transporter proteins or their mRNA between drug-resistant and drug-sensitive cancer cells.
• EV-mediated transfer of regulatory proteins and noncoding RNAs also contributes to the induction of MDR.
• The transfer of a drug-sensitive phenotype via EVs has been documented, alongside interactions between non-tumor and tumor cells impacting MDR.

Conclusions:

• EVs play a critical role in the intercellular transfer of cancer multidrug resistance.
• Understanding EV-mediated MDR mechanisms can identify novel druggable targets and therapeutic strategies.
• Further research into uninvestigated aspects of EV-cancer cell communication is warranted for developing innovative treatments.