title: Molecular Subtyping in Diffuse Large B Cell Lymphoma: Closer to an Approach of Precision Therapy.
abstract: It has become clear that there is immense biological heterogeneity in diffuse large B cell lymphoma (DLBCL). Developing technology has allowed better characterization of patient subsets at a molecular level, allowing for a link of phenotype and clinical outcomes to oncogenic mechanisms and biologic signatures. Cell of origin and double hit status are able to identify aggressive subsets, with molecular profiling allowing for a clearer understanding of biologic pathways that contribute to cellular resistance to conventional treatment in these subsets. Although the standard treatment for DLBCL remains R-CHOP or R-CHOP-like therapy at present, rational drug targets have been established with novel classes of drugs under investigation. In germinal center (GC) DLBCL, mechanisms of therapeutic interest include anti-apoptosis mediated by BCL-2, PI3K/AKT/mTOR, and EZH2, whereas drug interventions are directed at BCR, NF-κB, and/or JAK-STAT pathways in activated B cell (ABC) DLBCL. There is also evidence for cooperation of various oncogenic pathways in these subsets. As such, we are arguably on the verge of shifting to a more tailored approach using single and combinatorial strategies-this, however, relies on prioritizing the exploration of biomarkers for patient selection for validating novel treatment strategies.
authors.affiliation: Northwestern University Feinberg School of Medicine, 645 N Michigan Ave, Suite 1020, Chicago, IL, 60611-2927, USA. reem.karmali@northwestern.edu.|Robert H. Lurie Comprehensive Cancer Center, Chicago, IL, 60611, USA. reem.karmali@northwestern.edu.
authors.forename: Reem
authors.initials: R
authors.lastname: Karmali
authors.affiliation: Robert H. Lurie Comprehensive Cancer Center, Chicago, IL, 60611, USA.|Northwestern University Feinberg School of Medicine, 676 North St. Clair Street, Suite 850, Chicago, IL, 60611-2927, USA.
authors.forename: Leo I
authors.initials: LI
authors.lastname: Gordon
mesh_terms: D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D015415:Biomarkers; D003520:Cyclophosphamide / Q000627:therapeutic use; D004317:Doxorubicin / Q000627:therapeutic use; D004734:Energy Metabolism / Q000187:drug effects; D044127:Epigenesis, Genetic / Q000187:drug effects; D020869:Gene Expression Profiling / Q000379:methods; D020022:Genetic Predisposition to Disease; D006801:Humans; D056747:Immunomodulation / Q000187:drug effects; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis* / Q000235:genetics* / Q000628:therapy; D058990:Molecular Targeted Therapy; D057285:Precision Medicine / Q000379:methods; D011241:Prednisone / Q000627:therapeutic use; D000069283:Rituximab; D015398:Signal Transduction / Q000187:drug effects; D014750:Vincristine / Q000627:therapeutic use
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D015415:Biomarkers; C571759:R-CHOP protocol; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone
keywords: Apoptosis; CART; Checkpoint inhibition; DLBCL; Epigenetics; Immunotherapy