DNA Repair and cancer treatments
Detection of DNA Repair defects potentially increasing tumor mutational load.
Predict response to ImmunoTherapy
Identification of patients at risk of developing severe inflammation and adverse effects in response to radiotherapy.
DNA Repair inhibitors
We check that drugs effectively impact DNA Repair activities.
We check for activation of compensatory mechanisms.
Predict response to DNA Repair Inhibitors
Refinement of the mutation-based classification of tumors identifies patient subtypes. Verification of the drug's functional impact.
Predict response to Targeted Therapy
Classification of tumors based on their true DNA Repair capacities.
Identification of activities up regulated and down regulated to optimize therapeutic strategies.
LXRepair prospective clinical studies
Identifying early radiotoxicity biomarkers
Base Excision Repair regulation in particular is closely linked to inflammation.
LXRepair's RAD-LX signature, by integrating patient's oxidative stress defences and their inflammation status, can potentially predict radiotoxicity events.
Identifying chemo-radioresistance biomarkers in Head&Neck cancers
Several therapeutic options are available to patients with Head&Neck cancer. Surgery is indicated when the tumor is accessible.
For unresectable or non-operable tumors, induction chemotherapy (Cisplatin, 5-FU, Docetaxel) followed by radiotherapy or chemoradiotherapy is proposed. Other options include radiotherapy or chemoradiotherapy alone, or combinations. Treatment toxicity and intrinsic or acquired resistance limit the cure rate for patients .
We urgently need biomarkers to help select the best therapeutic option.
DNA Repair mechanisms are directly responsible for the tumor's response to these DNA-damaging therapies.
Given the complexity of the treatment and the complexity of DNA Repair mechanisms, single biomarkers are not informative enough.
LXRepair multiplex assays offer unmatched profiling solutions, providing a fuller understanding of the different cancer subtypes and allowing drivers of resistance and toxicity to treatments to be identified.
The SPOT-LX™ platform can identify relevant biomarkers from blood lymphocytes and tumor biopsies and predict treatment outcome.
The prospective ChemRadAssay clinical trial, conducted in collaboration with Hospice Civils de Lyon, Claude Bernard University, Grenoble Hospital and Centre Leon Bérard, aims to test this process.
ChemRad is supported by the CLARA Canceropole's "Preuve de Concept" program.
Improve stratification of melanoma
Resistance of melanoma to radiotherapy and chemotherapy is commonly attributed to specific regulation of DNA Repair.
Recent advances in our understanding of the molecular factors driving malignant transformation have led to the classification of melanoma based on specific gene mutations, and the development of targeted therapies. Notably, DNA Repair mechanisms are regulated by the MAPK/Pl3K/AKT signaling pathway.
The success of immunotherapy has further changed clinical management of melanoma. But patient responses to these treatments remain highly heterogeneous. There is thus a critical need to identify biomarkers to predict who will benefit from which therapy.
Exposure to UV radiation is a major risk factor for melanoma. Exposure to carcinogenic risk factors results in elevated mutation frequencies in tumors. Defective DNA Repair could be cause the elevated mutation frequencies observed in melanoma. Interestingly, the mutational load predicts a clinical benefit for immunotherapy in various cancers.
A unified strategy is required to class melanoma patients and direct selection of the most appropriate therapeutic option. Because of the central role played by DNA Repair in this carcinogen-induced tumor, we propose a new stratification based on functional DNA Repair analysis.
The first results obtained with melanoma patients confirmed that mutations in the MAPK pathways drive the DNA Repair Enzyme Signature, with some notable exceptions. Specific DNA Repair defects are detected in samples from some patients; these could lead to genomic instability and an elevated mutation load.
DX-kit pipeline overview
Assay predicting Radiotoxicity: CE-marking expected in 2020
Metastatic melanoma assay: Patent application filed on a new method of melanoma stratification to choose the best treatment
Head&Neck cancer assay: recruitments active (Preuve du Concept, cancéropole CLARA project)