Biomarker TFF1 for predicting effect of C-MET inhibitor

#This application claims the benefit of Korean Patent Application No. 10-2014-0008733 filed on Jan. 24, 2014 in the Korean Intellectual Property Office, the entire disclosure of which is hereby incorporated by reference.

#Incorporated by reference in its entirety herein is a computer-readable nucleotide/amino acid sequence listing submitted herewith and identified as follows: One 141,706 bytes ASCII (Text) file named “719249_ST25_revised.TXT” created Jun. 14, 2016.

#1. Field

#FIG. 1 is a set of graphs showing the proliferation level (cell viability) of lung cancer cell lines, when treated with an anti-c-Met antibody.

#FIG. 2 is a graph showing the level of TFF1 transcript in lung cancer cell lines, which is measured by qPCR and expressed as the difference between CT values of TFF1 and HPRT1 (CT value of TFF1-CT value of HPRT1).

#FIG. 3 provides graphs showing the proliferation level (cell viability) of MKN45 cells and anti-c-Met antibody resistance-induced MKN45 cells, when treated with an anti-c-Met antibody.

#Provided is a use of Trefoil factor 1 (TFF1) protein or TFF1 gene, or both, in predicting the effect of a c-Met inhibitor in a subject, and/or monitoring induced resistance against a c-Met inhibitor administered to a subject.

#Herein, the effect of a c-Met inhibitor may refer to the prevention, improvement, alleviation, and/or treatment of a c-Met related disease such as cancer. The effect of a c-Met inhibitor may refer to the effect of inhibiting proliferation of cancer cell or cancer tissue, killing cancer cells or cancer tissue, inhibiting migration and/or invasion of cancer cells, which is related to cancer metastasis, and the like.

#TFF1 is expressed in and secreted from digestive organs. Without wishing to be bound to a particular theory or mechanism of action, it is believed that the responsiveness of a c-Met related disease to a c-Met inhibitor differs depending on the TFF1 expression level in the diseased cells. Also, it is believed that the changing profile between TFF1 expression levels in cells with and without treatment with a c-Met inhibitor or before and after treatment with a c-Met inhibitor differs depending on the responsiveness of the cells to a c-Met inhibitor. In particular, when the level of TFF1 or TFF1 gene in a biological sample is low, it can be confirmed that a c-Met inhibitor such as an anti-c-Met antibody can successfully exhibit its effect on the biological sample or a subject from which the biological sample is obtained. In addition, when resistance to a c-Met inhibitor such as an anti-c-Met antibody is induced, it can be observed that the level of TFF1 or TFF1 gene is increased. Thus, TIFF1 expression can be used both to select a disease or patient suitable for treatment with a c-Met inhibitor, and to monitor the potential build-up of resistance to the c-Met inhibitor during treatment.