Multiple Myeloma: Available Therapies and Causes of Drug Resistance

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Multiple Myeloma: Available Therapies and Causes of Drug Resistance

Friday, 17.04.2020

Multiple myeloma is a rare debilitating hematologic malignancy of plasma cells, a type of immune cell responsible for producing antibodies. Abnormal accumulation of myeloma plasma cells within the bone marrow will result in the disruption of haematopoiesis (anaemia, infections), increased bone turnover (osteolytic lesions, hypercalcemia) and excessive amounts of monoclonal immunoglobular proteins (kidney failure). Even though multiple myeloma is treatable for a while, it still remains as an incurable disease with a severe impact in the patients’ quality of life.

Despite innovative myeloma treatment strides achieved in the last decade, all myeloma patients will develop acquired drug resistance and develop refractory relapse at some point.  In this manuscript, some members of the Cancer Drug Resistance group of i3S reviewed the main drugs used in multiple myeloma treatment and the main causes of drug resistance in these patients. Most importantly, these authors highlight the areas that need to be further clarified in order to identify novel therapeutic targets to counteract the acquired drug resistance in multiple myeloma patients.

 

Authors and Affiliations:

Vanessa Pinto1,2,3, Rui Bergantim1,2,4,5, Hugo R. Caires1,2, Hugo Seca1,2, José E. Guimarães1,2,4,5, M. Helena Vasconcelos1,2,6

1 i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal;

2Grupo Cancer Drug Resistance, IPATIMUP - Instituto de Patologia Molecular e Imunologia da Universidade do Porto, Porto, Portugal;

3FCTUC - Faculdade de Ciências e Tecnologia da Universidade de Coimbra, Coimbra, Portugal;

4 Hematologia Clínica, Hospital São João, Porto, Portugal;

5 Hematologia Clínica, Faculdade de Medicina, Universidade do Porto, Porto, Portugal;

6Departamento de Ciências Biológicas, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal.

 

Abstract:

Multiple myeloma (MM) is the second most common blood cancer. Treatments for MM include corticosteroids, alkylating agents, anthracyclines, proteasome inhibitors, immunomodulatory drugs, histone deacetylase inhibitors and monoclonal antibodies. Survival outcomes have improved substantially due to the introduction of many of these drugs allied with their rational use. Nonetheless, MM patients successively relapse after one or more treatment regimens or become refractory, mostly due to drug resistance. This review focuses on the main drugs used in MM treatment and on causes of drug resistance, including cytogenetic, genetic and epigenetic alterations, abnormal drug transport and metabolism, dysregulation of apoptosis, autophagy activation and other intracellular signalling pathways, the presence of cancer stem cells, and the tumor microenvironment. Furthermore, we highlight the areas that need to be further clarified in an attempt to identify novel therapeutic targets to counteract drug resistance in MM patients.

 

Journal: Cancers

 

Link: https://doi.org/10.3390/cancers12020407