Recent Advances in Strategies for Extracellular Matrix Degradation and Synthesis Inhibition for Improved Therapy of Solid Tumors

Abstract

Despite a great deal of efforts made by researchers and the advances in the technology, the treatment of cancer is very challenging. Significant advances in the field of cancer therapeutics have been made but due to the complexity of solid tumor microenvironment, specially their dense extracellular matrix (which makes the conditions favorable for cancer growth, metastasis and acts as a barrier to the chemotherapeutic drugs as well as nanomedicine), the treatment of solid tumors is difficult. Overexpression of extracellular matrix components such as collagen, hyaluronan and proteoglycans in solid tumor leads to high interstitial fluid pressure, hypoxia, vascular collapse and poor perfusion which hinder the diffusion and convection of the drugs into the tumor tissue. This leads to the emergence of drug resistance and poor antitumor efficacy of chemotherapeutics. A number of approaches are being investigated in order to modulate this barrier for improved outcome of cancer chemotherapy. In this review, recent advances in the various approaches for the modulation of the extracellular matrix barrier of the solid tumor are covered and significant findings are discussed in an attempt to facilitate more investigations in this potential area to normalize the tumor extracellular matrix for improving drug exposure to solid tumor.

Keywords: Solid tumor; collagen; extracellular matrix; hyaluronic acid; interstitial fluid pressure; nanomedicine.