Modulating Tumor Extracellular Matrix by Simultaneous Inhibition of Two Cancer Cell Receptors

The extracellular matrix (ECM) is involved in fundamental cellular processes and pathological progression of many diseases. While most research and current knowledge focuses on the processes of biological and mechanical changes in ECM signaling residing cancer cells to respond, little is known of the converse-of how cancer cells initiate the changes of ECM properties. Here, it is reported that blocking the cancer cell signaling leads to disruption of tumor ECM. Using recombinant proteins (RPs) and recombinant protein-drug conjugates (RPDCs) that simultaneously target both epidermal growth factor receptor and integrin, it is demonstrated that multireceptor-mediated active modulation of tumor ECM can inhibit and even reverse tumor remodeling of the physiological and structural microenvironment. These results not only provide insights into the regulatory roles of cancer cells in developing a protumoral microenvironment, but also introduce a new therapeutic platform or strategy to treat cancers.