Autophagy: A Potential Therapeutic Target to Tackle Drug Resistance in Multiple Myeloma

Area of Science:

• Oncology
• Cell Biology
• Molecular Medicine

Background:

• Multiple myeloma (MM) is a prevalent hematologic malignancy with increasing patient survival due to novel therapies.
• Drug resistance remains a significant challenge, particularly in relapsed or refractory MM cases.
• Autophagy, an intracellular degradation process, plays a critical role in the development of MM drug resistance.

Purpose of the Study:

• To review the role of autophagy as a survival mechanism in multiple myeloma drug resistance.
• To explore potential therapeutic strategies targeting autophagy to overcome drug resistance in MM.

Main Methods:

• Literature review of studies investigating autophagy in multiple myeloma.
• Analysis of mechanisms linking autophagy, High mobility group box protein 1 (HMGB1), proteasome suppression, and drug resistance.
• Examination of the role of autophagy inhibition in novel therapeutic approaches, such as clarithromycin.

Main Results:

• High mobility group box protein 1 (HMGB1)-dependent autophagy contributes to drug resistance in MM.
• Proteasome inhibition activates autophagy, inducing drug resistance.
• Autophagy blockage is a proposed mechanism for the efficacy of clarithromycin in MM treatment.

Conclusions:

• Autophagy is a critical survival strategy exploited by multiple myeloma cells to develop drug resistance.
• Targeting autophagy presents a promising therapeutic avenue to enhance MM cell death and improve susceptibility to existing treatments.