Despite significant progress in treating gastrointestinal (GI) cancers through surgical resection, chemotherapy, radiotherapy, and targeted therapy, the objective response rate (ORR) for immune checkpoint inhibitor (ICI) therapy remains low. Common biomarkers such as PD-L1 expression, tumor mutational burden (TMB), and microsatellite instability (MSI) often lack predictive precision or are applicable to only a small subset of patients. The new DNA damage response-related immune activation (DRIA) signature seeks to overcome these limitations by identifying a unique set of genes associated with DNA damage response (DDR) and immune activation.
A recent study (DOI: 10.20892/j.issn.2095-3941.2023.0303) conducted by a team of research from Xijing Hospital of Air Force Military Medical University and Peking University Cancer Hospital, published in December 2023 in the journal Cancer Biology & Medicine introduces the DRIA signature, a biomarker that predicts patient responses to ICI therapy in GI cancers. This breakthrough could significantly enhance personalized treatment strategies.
The DRIA signature comprises three genes (CXCL10, IDO1, and IFI44L), derived from existing DNA damage immune response assays. Researchers tested its predictive capabilities with clinical and gene expression data from two GI cancer cohorts. In the discovery cohort, patients with a high DRIA score demonstrated a response rate of 81.8% to ICI therapy, compared to 8.8% among those with a low score. Additionally, the DRIA signature outperformed other predictive markers like PD-L1 expression, TMB, and MSI.
The results suggest that the DRIA signature could become a reliable biomarker for guiding ICI therapy in GI cancers, potentially applicable to other types of cancer as well. According to Yongzhan Nie, the study's lead researcher, "DDR deficiency has emerged as a key factor in tumor immunogenicity. The DRIA signature offers a new way to predict which patients will respond favorably to ICI therapy, potentially leading to higher survival rates and reduced unnecessary treatments."
With the ability to more accurately predict which patients will benefit from ICI therapy, the DRIA signature could revolutionize the treatment of GI cancers, enabling improved patient stratification, personalized care plans, and better clinical outcomes. Its utility might also extend to other cancer types, opening doors for broader applications in oncology.
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References
DOI
10.20892/j.issn.2095-3941.2023.0303
Original Source URL
https://doi.org/10.20892/j.issn.2095-3941.2023.0303
Funding information
This study was supported by the National Natural Science Foundation of China (Grant Nos. 81972761 and 82202837) and the National Key R&D Program of China (Grant Nos. 2016YFC1303200 and 2022YFC2505100).
About Cancer Biology & Medicine
Cancer Biology & Medicine (CBM) is a peer-reviewed open-access journal sponsored by China Anti-cancer Association (CACA) and Tianjin Medical University Cancer Institute & Hospital. The journal monthly provides innovative and significant information on biological basis of cancer, cancer microenvironment, translational cancer research, and all aspects of clinical cancer research. The journal also publishes significant perspectives on indigenous cancer types in China. The journal is indexed in SCOPUS, MEDLINE and SCI (IF 5.5, 5 year IF 6.1), with all full texts freely visible to clinicians and researchers all over the world (http://www.ncbi.nlm.nih.gov/pmc/journals/2000/).