Activated interferon response from DNA damage in multiple myeloma cells contributes to the chemotherapeutic effects of anthracyclines

Frontiers in Oncology, Год журнала: 2024, Номер 14

Опубликована: Май 10, 2024

Introduction Multiple myeloma (MM) is a malignant plasma cell disease caused by abnormal proliferation of clonal cells in bone marrow. Upfront identification tumor subgroups with specific biological markers has the potential to improve biologically-driven therapy. Previously, we established molecular classification stratifying multiple into two subtypes different prognosis based on gene module co-expressed MCL-1 (MCL1-M). Methods Gene Ontology (GO) analysis differentially expressed genes was performed identify signal pathway. Drug sensitivity analyzed using OncoPredict algorithm. lines detected CCK8 and flow cytometry. RNA-seq drug-sensitive before after adriamycin treatment. RT-qPCR used further verify sequencing results. The expression γ-H2AX dsDNA sensitive resistant immunofluorescence method. Results In our study, demonstrated that MCL1-M low MM were more anthracyclines. We treated doxorubicin vitro discovered association drug IFN signaling. Herein, demonstrate doxorubicin-sensitive line showed significant DNA damage up-regulated related response, which not observed drug-insensitive lines. Discussion Our results suggest active signaling pathway may serve as marker for predicting chemotherapy patients myeloma. With system, can screen potentially good response interferon provide individualized treatment MM. propose IFN-a adjuvant therapy anthracyclines therapeutic effect prolong survival patients.

Язык: Английский

At the Crossroads of the cGAS-cGAMP-STING Pathway and the DNA Damage Response: Implications for Cancer Progression and Treatment

Pharmaceuticals, Год журнала: 2023, Номер 16(12), С. 1675 - 1675

Опубликована: Дек. 1, 2023

The evolutionary conserved DNA-sensing cGAS-STING innate immunity pathway represents one of the most important cytosolic systems that is activated in response to viral invasion and/or damage integrity nuclear envelope. key outcome this production interferon, which subsequently stimulates transcription hundreds genes. In oncology, situation complex because may serve either anti- or pro-oncogenic roles, depending on context. prevailing understanding when immune by sensing DNA, such as DNA released from ruptured micronuclei, it results attracts cytotoxic cells destroy tumors. However, tumor have adjusted significant chromosomal instability, particularly relapsed, treatment-resistant cancers, often supports cancer progression, fostering epithelial-to-mesenchymal transition (EMT). Here, we review intricate terms its association with giving special attention pancreatic ductal adenocarcinoma and gliomas. As development new cGAS-STING-modulating small molecules immunotherapies oncolytic viruses involves serious challenges, highlight several recent fundamental discoveries, proton-channeling function STING. These discoveries guiding lights for potential pharmacological advancements.

Язык: Английский