Drug-Resistance Mechanism and New Targeted Drugs and Treatments of Relapse and Refractory DLBCL

Zhang, Jing; Gu, Yan; Chen, Baoan

doi:10.2147/cmar.s400013

Cited by 15 publications

(8 citation statements)

References 98 publications

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“…Diffuse large B-cell lymphoma is a heterogeneous group of aggressive lymphoma that has specific clinical course and response to therapy. 75 , 76 As a result, DLBCL is still remained challenging for physicians in developing specific targeted treatments for patients care. Recurrent mutations such as splicing mutation associated with poor clinical outcomes in DLBCL.…”

Section: Splicing Mutation and Targeted Drugs For The Treatment Of Dlbclmentioning

confidence: 99%

Role of RNA Splicing Mutations in Diffuse Large B Cell Lymphoma

Berta,

Girma,

Melku

et al. 2023

IJGM

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Ribonucleic acid splicing is a crucial process to create a mature mRNA molecule by removing introns and ligating exons. This is a highly regulated process, but any alteration in splicing factors, splicing sites, or auxiliary components affects the final products of the gene. In diffuse large B-cell lymphoma, splicing mutations such as mutant splice sites, aberrant alternative splicing, exon skipping, and intron retention are detected. The alteration affects tumor suppression, DNA repair, cell cycle, cell differentiation, cell proliferation, and apoptosis. As a result, malignant transformation, cancer progression, and metastasis occurred in B cells at the germinal center. B-cell lymphoma 7 protein family member A (BCL7A), cluster of differentiation 79B (CD79B), myeloid differentiation primary response gene 88 (MYD88), tumor protein P53 (TP53), signal transducer and activator of transcription (STAT), serum- and glucose-regulated kinase 1 (SGK1), Pou class 2 associating factor 1 (POU2AF1), and neurogenic locus notch homolog protein 1 (NOTCH) are the most common genes affected by splicing mutations in diffuse large B cell lymphoma.

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Section: Splicing Mutation and Targeted Drugs For The Treatment Of Dlbclmentioning

confidence: 99%

Role of RNA Splicing Mutations in Diffuse Large B Cell Lymphoma

Berta,

Girma,

Melku

et al. 2023

IJGM

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show abstract

“…However, 30% to 40% of patients are unresponsive or relapse, leading to a poor prognosis with a 2-year overall survival (OS) of only 20% to 40%. 26 The development and application of CAR-T-cell therapy offer new hope for the treatment of R/R DLBCL.…”

Section: Where Are We Now?mentioning

confidence: 99%

CAR-T cell therapy: Where are we now, and where are we heading?

Wang,

Wang

2023

Blood Science

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Chimeric antigen receptor (CAR)-T-cell therapies have exhibited remarkable efficacy in the treatment of hematologic malignancies, with 9 CAR-T-cell products currently available. Furthermore, CAR-T cells have shown promising potential for expanding their therapeutic applications to diverse areas, including solid tumors, myocardial fibrosis, and autoimmune and infectious diseases. Despite these advancements, significant challenges pertaining to treatment-related toxic reactions and relapses persist. Consequently, current research efforts are focused on addressing these issues to enhance the safety and efficacy of CAR-T cells and reduce the relapse rate. This article provides a comprehensive overview of the present state of CAR-T-cell therapies, including their achievements, existing challenges, and potential future developments.

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“…The integration of anti-CD20 rituximab (R) into the CHOP regimen and anti-CD79b polatuzumab (Pola) has marked a significant advancement in DLBCL therapy. However, the persistence of treatment-resistant and relapsed cases emphasizes the need for further research [ 20 , 21 , 22 , 23 , 24 , 25 ], and TME is a key factor in DLBCL progression, while interaction between DLBCL cells and various TME components, including macrophages, is closely linked to drug resistance [ 26 , 27 , 28 , 29 ].…”

Section: Introductionmentioning

confidence: 99%

Serum-Soluble CD163 Levels as a Prognostic Biomarker in Patients with Diffuse Large B-Cell Lymphoma Treated with Chemoimmunotherapy

Koudouna,

Gkioka,

Gkiokas

et al. 2024

IJMS

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The majority of patients with Diffuse Large B-cell Lymphoma (DLBCL) will respond to first-line treatment and be cured. However, the disease is heterogeneous, and biomarkers able to discriminate patients with suboptimal prognosis are needed. M2 CD163-positive tumor-associated macrophages (TAMs) were shown to be implicated in DLBCL disease activity regulation. Serum-soluble CD163 (sCD163) functions as a scavenger receptor for haptoglobin–hemoglobin complexes and is mostly expressed by monocytes and macrophages. Its levels are used to determine macrophage activation. We aimed to determine serum sCD163 in a sample of DLBCL patients and study eventual correlations with parameters of disease activity or survival. Serum sCD163 levels were measured in 40 frozen sera from patients diagnosed with DLBCL and 30 healthy individuals (HIs) using an enzyme-linked immunosorbent assay (ELISA). Statistical analyses were performed using SPSS version 28. The results showed that patients who achieved complete response after standard-of-care immunochemotherapy and were alive and disease-free after 12 months of follow-up but had elevated sCD163 levels (above median) at diagnosis presented a significantly worse overall survival compared to those with initial serum sCD163 levels below the median (p = 0.03). Consequently, serum sCD163 levels in patients with DLBCL may constitute a marker of long-term response to chemoimmunotherapy.

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Drug-Resistance Mechanism and New Targeted Drugs and Treatments of Relapse and Refractory DLBCL

Cited by 15 publications

References 98 publications

Role of RNA Splicing Mutations in Diffuse Large B Cell Lymphoma

Role of RNA Splicing Mutations in Diffuse Large B Cell Lymphoma

CAR-T cell therapy: Where are we now, and where are we heading?

Serum-Soluble CD163 Levels as a Prognostic Biomarker in Patients with Diffuse Large B-Cell Lymphoma Treated with Chemoimmunotherapy

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