Combination for treating cancer

The present invention relates to the treatment of cancer and particularly of lung cancer. In the present study, the inventors analyzed the role of the Notch pathway in EGFR-driven lung adenocarcinoma (LUAD) using complex genetic mouse models and patient derived xenografts. They found that, similarly to KRAS-driven LUAD, EGFR-driven LUAD shows both Notch pathway hyperactivation and addiction to its activity. Importantly, combination of EGFR tyrosine Kinase Inhibitors (TKIs) with Notch inhibition re-sensitizes LUAD cells harboring gatekeeper mutations EGFRT790M or EGFRC797S to gefitinib and osimertinib, respectively. Moreover, they show that pSTAT3, which is known to increase upon EGFR TKI treatment, directly binds to the HES1 promoter and represses HES1 expression. Finally, high HES1 expression levels correlate with shorter progression free survival and its expression increases upon progression in EGFR mutated patients under TKI treatment. Thus, the present invention relates to a combination of a tyrosine-kinase inhibitor (TKI) against epidermal growth factor receptor (EGFR) and an inhibitor of the Notch signalling pathway for use in the treatment of a cancer in a subject in need thereof.

Patent Application number: European Procedure (Patents) (EPA) - 19 Juil. 2018 - 18 305 991.4
Inventors:
MARAVER AntonioBOUSQUET Emilie

Reference:

BIO17398-T1

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Aymeric Empereur
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Patent filling date: 19-07-2018
Rare disease: No
Second indication: No

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