R-CHOP resistance in diffuse large B-cell lymphoma: biological and molecular mechanisms.
10.1097/CM9.0000000000001294
- VernacularTitle:R-CHOP resistance in diffuse large B-cell lymphoma: biological and molecular mechanisms
- Author:
Liang WANG
1
;
Lin-Rong LI
2
Author Information
1. Department of Hematology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China.
2. Department of Breast Surgery, Peking Union Medical College Hospital, Beijing 100730, China.
- Publication Type:Review
- MeSH:
Antineoplastic Combined Chemotherapy Protocols/therapeutic use*;
Cyclophosphamide/therapeutic use*;
Doxorubicin/therapeutic use*;
Humans;
Lymphoma, Large B-Cell, Diffuse/genetics*;
Phosphatidylinositol 3-Kinases;
Prednisone/therapeutic use*;
Prognosis;
Rituximab/therapeutic use*;
Tumor Microenvironment;
Vincristine/therapeutic use*
- From:
Chinese Medical Journal
2020;134(3):253-260
- CountryChina
- Language:English
-
Abstract:
Although the first-line rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone regimen (R-CHOP) substantially improved outcomes for patients with diffuse large B-cell lymphoma (DLBCL), 40% of the patients suffered from relapsed/refractory disease and had poor survival outcomes. The detailed mechanism underlying R-CHOP resistance has not been well defined. For this review, we conducted a thorough search for literature and clinical trials involving DLBCL resistance. We discussed DLBCL biology, epigenetics, and aberrant signaling of the B-cell receptor (BCR), phosphatidylinositol 3-kinase (PI3K)/Akt, nuclear factor kappa light chain enhancer of activated B-cells (NF-κB), and the Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) pathways as defining mechanisms of DLBCL heterogeneity and R-CHOP resistance. The cell of origin, double- or triple-hit lymphoma and double-protein-expression, clonal evolution, tumor microenvironment, and multi-drug resistance help to contextualize DLBCL resistance in an (epi)genetically and biologically comparative manner. With better understanding of the biological and molecular landscape of DLBCL, a more detailed classification system and tailored treatments will ideally become available to further improve the prognosis of DLBCL patients.
