Targeting EGFR-driven Signaling of MMP-2 Secretion for the Management of Metastatic Cancers: Cellular and Molecular Aspects

Several cancers report overexpression of epidermal growth factor (EGF) receptors (EGFR). Similarly, an increase in the expression of matrix metalloproteinases (MMPs) was witnessed in the majority of metastatic and invasive carcinomas. MMPs facilitate the activation of signaling pathways that regulate angiogenesis, inflammation, and cell proliferation. They also act as regulators of the tumor microenvironment (TME), are implicated in the migration of cancer cells, and enhance extracellular matrix turnover (ECM). Various reports suggest that the EGFR expression interplays with the production of MMP-2 transcriptionally and translationally, emphasizing the need to target both proteins to combat metastatic carcinoma. The present chapter focuses essentially on the role of EGFR and MMP-2 during carcinoma, their transcriptional factors involved in downstream signaling, and crucial inhibitors. Utilizing the expression level of MMPs as a diagnostic and prognostic biomarker along with developing newer MMP/EGFR dual targeting inhibitors would increase the drug's effectiveness.