The present invention provides MT4-MMP inhibitor and EGFR inhibitor for use in the treatment of cancer, wherein said MT4-MMP inhibitor and EGFR inhibitor are different from each other. MT4-MMP (MMP-17) is a glycosylphosphatidyl inositol (GPI) anchored MMP produced by cancer cells that promotes tumor vascularization and metastases. The present invention found that MT4-MMP expression promotes cancer cell proliferation. These effects involve retinoblastoma protein (Rb) inactivation, cyclin dependent kinase CDK4 activation and Epidermal Growth Factor Receptor (EGFR) signaling. Co-immuno-precipitations indicate the existence of protein complexes harboring MT4-MMP and EGFR. The present invention further found a novel mechanism of MT4-MMP action through an outside-in signaling involving EGFR. An unexpected crosstalk between an MMP and EGFR was identified and recognized as a key driver of cancer cell biology.