Boehringer Ingelheim International Gmbh

Ulrich Hirt

Harald Engelhardt

Heinz Stadtmueller

Otmar Schaaf

Irene Waizenegger

Guido Boehmelt

Guenther Adolf

Pilar Garin-Chesa

The present invention relates to a method for determining whether a cancer patient is susceptible to treatment with a protein tyrosine kinase 2 (PTK2) inhibitor, comprising detecting the expression of the E-cadherin protein in a cancer sample of said cancer patient, wherein an E-cadherin protein immunoreactivity score (IRS) of 0-2 indicates that the cancer patient is susceptible to treatment with a PTK2 inhibitor. Said detection of the expression of the E-cadherin protein in a cancer sample of a cancer patient is preferably conducted by way of an immunohistochemistry (IHC) method. Said IHC method preferably employs a primary antibody which is specific for E-cadherin and a secondary antibody which specifically reacts with the primary antibody. The present invention also relates to a method of treating a cancer patient whose cancer is characterized by an E-cadherin protein immunoreactivity score (IRS) of 0-2, comprising administering to the patient a therapeutically effective amount of a PTK2 inhibitor. In a further aspect, the present invention relates to a PTK2 inhibitor for use in the treatment of a cancer patient whose cancer is characterized by an E-cadherin protein immunoreactivity score (IRS) of 0-2. The present invention also provides a method of screening for a therapeutically effective PTK2 inhibitor comprising the steps of (a) providing cancer cells or a cancer cell line which are characterized by an E-cadherin protein immunoreactivity score of 2, 1, or 0 (1 being preferred and 0 being even more preferred); (b) contacting the cancer cell or the cancer cell line of (a) with a PTK2 inhibitor; and (c) evaluating whether the PTK2 inhibitor negatively affects the cancer cell/cancer cell lines. In a further aspect, the present invention relates to a method for stratifying cancer patients that are susceptible to treatment with a PTK2 inhibitor, comprising determining the E-cadherin IRS score in a cancer sample of said patient, wherein an E-cadherin protein immunoreactivity score (IRS) of 0-2 (i.e. 2, 1, or 0) indicates that the cancer patient is susceptible to treatment with a PTK2 inhibitor. The present invention also relates to a pharmaceutical package comprising a PTK2 inhibitor, and (a) instructions and/or an imprint indicating that said PTK2 inhibitor is to be used for the treatment of patients which suffer from a cancer which is characterized by an E-cadherin protein immunoreactivity score of 2, 1, or 0 (1 being preferred and 0 being more preferred); and/or (b) instructions and/or an imprint indicating that said patient is to be stratified by a method of the present invention; and/or (c) means to carry out a method as defined herein.

Stratification of pancreatic and ovarian cancer patients for susceptibility to therapy with PTK2 inhibitors

The present invention encompasses compounds of general formula (1) whereinR, Rand Rare defined as in claim, which are suitable for the treatment of diseases characterized by excessive or abnormal cell proliferation, and their use for preparing a pharmaceutical composition having the above-mentioned properties.

Substituted 9H-purin-2-YL compounds, compositions thereof and uses thereof

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Ummendorf, Austria

Ulrich Hirt