DDIR (DNA Damage Immune Response)

Almac DDIR – A predictive signature for DNA Damaging Agents and Immuno-Oncology

Almac has developed a 44 transcript RNA based gene expression signature (formerly known as DDRD) that detects a subgroup of tumors that have activation of immune signaling in response to genomic instability/ associated with loss of the Fanconi Anemia (FA)/ BRCA pathway.

The Underlying Biology 

The DDIR molecular subtype represents tumors with a loss of function of the FA/BRCA pathway, a key response mechanism to stalled DNA replication in the S-phase of the cell cycle. A loss in the FA/ BRCA pathway or exogenous DNA damage can cause an accumulation of the cytosolic DNA sensor cGAS, activating the STING/TBK1/IRF3 innate immune response. Constitutive activation of the cGAS pathway stimulates the immune transcription of chemokines CXCL10 and CCL5. Consequently, an infiltration of interferon-related genes including T-cell specific ligands such as CD4+ and CD8+ are seen in the epithelial region of DDIR positive tumors.

Application

The DDIR signature can be applied to formalin fixed paraffin embedded (FFPE) tumor specimens across multiple disease indications (breast, ovarian, oesophageal, prostate and others). Discovery and validation of this signature has been published in various scientific journals. (See related resources below).

Considering the underlying biology of the signature, DDIR branches into two main utilities:

 

Almac’s DDIR signature has the potential to be used as a companion diagnostic for either utility across a range of disease areas.

Contact Us

Assessment of the Almac DDIR Signature can be made through use of Almac Diagnostic Services unique gene expression report, claraT. This provides visualization of the DDIR signature scores as an easy-to-interpret graduated bar within the Avoiding Immune Destruction and Genome Instability & Mutation Hallmarks of Cancer.

Related resources

  • Validation of the DNA Damage Immune Response Signature in Patients With Triple-Negative Breast Cancer From the SWOG 9313c Trial

    Publication

    Validation of the DNA Damage Immune Response Signature in Patients With Triple-Negative Breast Cancer From the SWOG 9313c Trial

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  • Activation of STING-Dependent Innate Immune Signaling By S-Phase-Specific DNA Damage in Breast Cancer

    Publication

    Activation of STING-Dependent Innate Immune Signaling By S-Phase-Specific DNA Damage in Breast Cancer

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  • Almac Group Discover an Exciting Link between its Immune Response Assay and Checkpoint Inhibitor Based Therapy

    News

    Almac Group Discover an Exciting Link between its Immune Response Assay and Checkpoint Inhibitor Based Therapy

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  • Publications

    Identification and Validation of an Anthracycline / Cyclophosphamide–Based Chemotherapy Response Assay

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  • News

    Almac publishes breast cancer chemotherapy response assay in the Journal of the National Cancer Institute

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  • Poster

    DNA Damage Response Deficiency Assay predicts response to treatment in ovarian cancer

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  • Poster

    Identification of a novel breast cancer molecular subgroup associated with a deficiency in DNA-damage response

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  • Poster

    Impact of DNA Repair Deficiency Signature on Outcomes in Triple Negative Breast Cancer (TNBC) Patients Treated with AC Chemotherapy

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  • Poster

    Association of a DNA Damage Response Deficiency (DDRD) Assay with Prognosis in Resected Esophageal and Gastric Adenocarcinoma

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