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Autophagy and Apoptosis: Current Challenges of Treatment and Drug Resistance in Multiple Myeloma
Omar S Al-Odat1,2, Daniel A Guirguis1, Nicole K Schmalbach1
1Department of Biomedical Sciences, Cooper Medical School of Rowan University, Camden, NJ 08103, USA.
Abstract:
Over the past two decades, the natural history of multiple myeloma (MM) has evolved dramatically, owing primarily to novel agents targeting MM in the bone marrow microenvironment (BMM) pathways. However, the mechanisms of resistance acquisition remain a mystery and are poorly understood. Autophagy and apoptosis are tightly controlled processes and play a critical role in the cell growth, development, and survival of MM. Genetic instability and abnormalities are two hallmarks of MM. During MM progression, plasma malignant cells become genetically unstable and activate various signaling pathways, resulting in the overexpression of abnormal proteins that disrupt autophagy and apoptosis biological processes. Thus, achieving a better understanding of the autophagy and apoptosis processes and the proteins that crosslinked both pathways, could provide new insights for the MM treatment and improve the development of novel therapeutic strategies to overcome resistance. This review presents a sufficient overview of the roles of autophagy and apoptosis and how they crosslink and control MM progression and drug resistance. Potential combination targeting of both pathways for improving outcomes in MM patients also has been addressed.
Insights
Understanding autophagy and apoptosis in multiple myeloma (MM) is key to overcoming drug resistance. Targeting these processes offers new therapeutic strategies for MM patients.
Area of Science:
- Hematology
- Cancer Biology
- Molecular Oncology
Background:
- Multiple myeloma (MM) treatment has advanced with novel agents targeting the bone marrow microenvironment.
- Mechanisms of drug resistance in MM remain poorly understood.
- Autophagy and apoptosis are critical cellular processes implicated in MM progression and survival.
Purpose of the Study:
- To review the roles of autophagy and apoptosis in multiple myeloma.
- To explore the cross-linking mechanisms between autophagy and apoptosis in MM.
- To discuss therapeutic strategies targeting these pathways for overcoming drug resistance.
Main Methods:
- Literature review focusing on autophagy, apoptosis, and multiple myeloma.
- Analysis of signaling pathways involved in MM progression and drug resistance.
- Synthesis of current knowledge on the interplay between autophagy and apoptosis in MM.
Main Results:
- Genetic instability in MM progression leads to aberrant protein expression disrupting autophagy and apoptosis.
- Dysregulation of autophagy and apoptosis contributes to therapeutic resistance in MM.
- Proteins cross-linking autophagy and apoptosis pathways are crucial in MM pathogenesis.
Conclusions:
- A deeper understanding of autophagy and apoptosis interplay is vital for novel MM treatment development.
- Targeting both autophagy and apoptosis pathways holds promise for improving outcomes in MM patients.
- Combination therapies focusing on these pathways could overcome drug resistance in multiple myeloma.
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