Please use this identifier to cite or link to this item: https://doi.org/10.3390/biom12091261
Title: Molecular Determinants Underlying the Anti-Cancer Efficacy of CD38 Monoclonal Antibodies in Hematological Malignancies
Authors: Mustafa, Nurulhuda 
Azaman, Muhamad Irfan 
Ng, Giselle GK
Chng, Wee Joo 
Keywords: Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
CD38
immunotherapy
blood malignancies
daratumumab
drug combination
extracellular vesicles
miRNA
CHRONIC LYMPHOCYTIC-LEUKEMIA
MULTIPLE-MYELOMA CELLS
T-CELL
RETINOIC ACID
OPEN-LABEL
REGULATORY CELLS
MUTATION STATUS
FLOW-CYTOMETRY
B-CLL
EXPRESSION
Issue Date: 1-Sep-2022
Publisher: MDPI
Citation: Mustafa, Nurulhuda, Azaman, Muhamad Irfan, Ng, Giselle GK, Chng, Wee Joo (2022-09-01). Molecular Determinants Underlying the Anti-Cancer Efficacy of CD38 Monoclonal Antibodies in Hematological Malignancies. BIOMOLECULES 12 (9). ScholarBank@NUS Repository. https://doi.org/10.3390/biom12091261
Abstract: CD38 was first discovered as a T-cell antigen and has since been found ubiquitously expressed in various hematopoietic cells, including plasma cells, NK cells, B cells, and granulocytes. More importantly, CD38 expression levels on malignant hematopoietic cells are significantly higher than counterpart healthy cells, thus presenting itself as a promising therapeutic target. In fact, for many aggressive hematological cancers, including CLL, DLBCL, T-ALL, and NKTL, CD38 expression is significantly associated with poorer prognosis and a hyperproliferative or metastatic phenotype. Studies have shown that, beyond being a biomarker, CD38 functionally mediates dysregulated survival, adhesion, and migration signaling pathways, as well as promotes an immunosuppressive microenvironment conducive for tumors to thrive. Thus, targeting CD38 is a rational approach to overcoming these malignancies. However, clinical trials have surprisingly shown that daratumumab monotherapy has not been very effective in these other blood malignancies. Furthermore, extensive use of daratumumab in MM is giving rise to a subset of patients now refractory to daratumumab treatment. Thus, it is important to consider factors modulating the determinants of response to CD38 targeting across different blood malignancies, encompassing both the transcriptional and post-transcriptional levels so that we can diversify the strategy to enhance daratumumab therapeutic efficacy, which can ultimately improve patient outcomes.
Source Title: BIOMOLECULES
URI: https://scholarbank.nus.edu.sg/handle/10635/234467
ISSN: 2218-273X
DOI: 10.3390/biom12091261
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