Autophagy and Apoptosis: Current Challenges of Treatment and Drug Resistance in Multiple Myeloma

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.

Knockdown of BAP31 Overcomes Hepatocellular Carcinoma Doxorubicin Resistance through Downregulation of Survivin

“…Apoptosis is a common mechanism of drug-induced tumor cell death, and altered apoptosis pathways are some of the important mechanisms underlying the development of the chemoresistance of cancer cells [36,37]. Studies have shown that apoptosis signaling pathways influence chemosensitivity.…”

Exploring the role of histone deacetylase and histone deacetylase inhibitors in the context of multiple myeloma: mechanisms, therapeutic implications, and future perspectives

“…Their ability to target both epigenetic and non-epigenetic factors highlights their promise in MM treatment, especially when used alongside other therapies [ 30 ]. Moreover, autophagy, an essential cellular mechanism responsible for the degradation and recycling of impaired organelles and proteins, assumes a multifaceted and ambivalent role in the pathology of MM [ 40 , 50 , 51 ]. This process facilitates cellular survival under conditions of stress by provisioning vital nutrients and energy, thereby contributing to the development of drug resistance.…”

Design, synthesis, and activity evaluation of 2-iminobenzimidazoles as c-Myc inhibitors for treating multiple myeloma

“…Multiple myeloma (MM), the second most common blood cancer, is a plasma cell malignancy frequently accompanied by hypercalcemia, immune dysfunction, and renal failure [ [1] , [2] , [3] ]. Despite the employment of various therapeutic methods, such as immunomodulatory agents, proteasome inhibitors, and autologous stem cell transplantation (ASCT), MM remains an incurable disease with nearly 160,000 new cases and 106,000 deaths annually [ 4 , 5 ].…”