The post-chemotherapy changes of tumor physical microenvironment: Targeting extracellular matrix to address chemoresistance

The tumor physical microenvironment (TPME) contributes to cancer chemoresistance in both mechanical and mechanobiological approaches. Along with chemotherapy, the tumor microenvironment undergoes dramatic changes, most of which can regulate TPME through extracellular matrix (ECM) remodeling and related signaling pathways. However, there is still no discussion about the post-chemotherapy TPME changes mediated by ECM remodeling, and consequent impact on chemoresistance. Herein, we summarize the TPME alterations induced by chemotherapy and corresponding influence on chemotherapy response of cancer cells in context of ECM. The response of cancer cell to chemotherapy, imposed by post-chemotherapy ECM, are discussed in both mechanical (ECM physical features) and mechanobiological (ECM-responsive signaling pathways) manner. In the end, we present ECM remodeling and related signaling pathways as two promising clinic strategies to relieve or overcome chemoresistance induced by TPME change, and summarize the corresponding therapeutic agents currently being tested in clinical trials.