Background: Although most patients with diffuse large B-cell lymphoma (DLBCL) achieve complete remission after first-line rituximab-containing immunochemotherapy, up to 40% of patients relapse and require salvage therapy. Among those patients, a substantial proportion remain refractory to salvage therapy due to insufficient efficacy or intolerance of toxicities. A hypomethylating agent, 5-azacytidine, showed a chemosensitizing effect when primed before chemotherapy in lymphoma cell lines and newly diagnosed DLBCL patients. However, its potential to improve outcomes of salvage chemotherapy in DLBCL has not been investigated.
Results: In this study, we demonstrated the mechanism of 5-azacytidine priming as a chemosensitizer in a platinum-based salvage regimen. This chemosensitizing effect was associated with endogenous retrovirus (ERV)-induced viral mimicry responses via the cGAS-STING axis. We found deficiency of cGAS impaired the chemosensitizing effect of 5-azacytidine. Furthermore, combining vitamin C and 5-azacytidine to synergistically activate STING could be a potential remedy for insufficient priming induced by 5-azacytidine alone.
Conclusions: Taken together, the chemosensitizing effect of 5-azacytidine could be exploited to overcome the limitations of the current platinum-containing salvage chemotherapy in DLBCL and the status of cGAS-STING has the potential to predict the efficacy of 5-azacytidine priming.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10155448 | PMC |
| http://dx.doi.org/10.1186/s13148-023-01493-x | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
A Canadian Perspective on Systemic Therapy for Recurrent or Metastatic Nasopharyngeal Carcinoma.
Curr Oncol
January 2025
Department of Medical Oncology, Arthur JE Child Comprehensive Centre, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 5G2, Canada.
Although the majority of patients with nasopharyngeal carcinoma (NPC) present with early-stage or locoregional disease that can be treated with definitive radiotherapy, approximately 20% of patients experience disease recurrence, and 15% present with metastatic disease that is not amenable to curative therapy. Management of patients with recurrent or metastatic (r/m) NPC who are not candidates for local salvage therapy is challenging in Canada, as there is uncertainty in extrapolating evidence that is largely generated from Southeast China to non-endemic regions such as Canada. Currently, treatment options in Canada are limited to chemotherapy regimens that can only achieve short-term response and prolongation of survival.
View Article and Find Full Text PDFForequarter amputation: a viable approach for salvaging lives in chemoresistant upper limb bone tumours.
BMJ Case Rep
January 2025
Orthopaedics, All India Institute of Medical Science - Bhopal, Bhopal, Madhya Pradesh, India.
This case revolves around a mid-childhood boy diagnosed with a chemoresistant chondroblastic osteosarcoma, a rare and aggressive form of bone tumour affecting his left proximal humerus. Histopathological confirmation of chondroblastic osteosarcoma was obtained through core-needle biopsy. Despite initiating cytoreductive neoadjuvant chemotherapy using a vincristine and cyclophosphamide regimen, the tumour exhibited resistance, prompting the decision to proceed with a forequarter amputation.
View Article and Find Full Text PDFVenetoclax and azacitidine in combination with homoharringtonine, cytarabine, and aclarubicin for salvage therapy of relapsed/refractory T cell acute lymphoblastic leukemia.
Int J Hematol
January 2025
Department of Hematology, The 920th Hospital of Joint Logistics Support Force, No.212, Da Guan Road, Xishan District, Kunming, 650100, Yunnan, China.
Background: The treatment of relapsed/refractory T cell acute lymphoblastic leukemia (R/R T-ALL) is a significant challenge in hematologic oncology, and no standard salvage treatment plan exists. Both Chinese and international clinical guidelines recommend combination chemotherapy including venetoclax.
Methods: Efficacy and safety of venetoclax, azacitidine, homoharringtonine, cytarabine, and aclarubicin (VA-HAA) combination therapy were retrospectively analyzed in 3 patients with R/R T-ALL at the Department of Hematology, 920th Hospital of the Joint Logistics Support Force, Chinese People's Liberation Army.
AntiCD30-Conjugated Antibody Plus Standard BEAM as Conditioning Regimen for Autologous Hematopoietic Stem Cell Transplantation in Systemic Anaplastic Large Cell Lymphoma.
Hematol Rep
January 2025
Operations Department, Burjeel Medical City, Abu Dhabi 92510, United Arab Emirates.
The outcome of refractory/relapsed systemic Anaplastic Large Cell Lymphoma (R/R-sALCL), especially for anaplastic lymphoma kinase-1 (ALK-1)-negative disease, remains dismal even after autologous hematopoietic stem cell transplantation (AHSCT). The intensification of both salvage and conditioning regimens, without increasing the toxicity, could improve the outcome of AHSCT in R/R-sALCL. Based on the successful experience of the incorporation of antiD20 monoclonal antibodies in the treatment of B-Cell Lymphomas, we designed a salvage and conditioning regimen incorporating the antiCD30-conjugated antibody (Brentuximab Vedotin, BV) to standard chemotherapy regimens, and we describe herein the clinical course of a patient with AKL-ve, R/R-sALCL, who received salvage regimen BV + DHAP, followed by AHSCT with preparative regimen consisted of BV plus standard BEAM.
View Article and Find Full Text PDFCost-minimization analysis of the GORTEC 2014-04 randomized phase II study of stereotactic ablative radiotherapy (SABR) or chemotherapy-SABR in oligometastatic head and neck cancer.
Radiother Oncol
January 2025
GORTEC 4 bis rue Emile Zola 37000 Tours, France; Department of Radiotherapy, Centre François-Baclesse, Corpuscular Physics Laboratory, IN2P3, ENSICAEN, CNRS UMR 6534, Université de Normandie, Caen, France. Electronic address:
Purpose: The randomized phase II GORTEC 2014-04 and French Head and Neck Intergroup study showed deeper deterioration of the quality of life (HRQoL) and dramatically higher severe toxicity rates with similar overall survival rates using chemo-SABR compared to SABR alone in oligometastatic head and neck cancer (HNSCC) patients. We evaluated the costs associated with SABR-alone versus chemo-SABR and their associated costs (transportation, hospitalizations, etc).
Materials And Methods: 69 HNSCC patients with 1-3 oligometastases and a controlled primary were randomized from September 2015 to October 2022.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!