The following is a summary of “Post-chemotherapy changes of tumor physical microenvironment: Targeting extracellular matrix to address chemoresistance,” published in the December 2023 issue of Oncology by Li et al.

The tumor microenvironment, comprised of the extracellular matrix (ECM) and surrounding cellular components, is pivotal in influencing cancer progression and treatment response. Chemotherapy, while effectively targeting cancer cells, induces substantial modifications within this microenvironment. These alterations encompass ECM composition, structure, and associated signaling pathways, affecting the tumor surroundings’ biomechanical properties and biochemical cues.

However, current discussions rarely encompass the profound implications of these post-chemotherapy microenvironmental changes, particularly about ECM remodeling and their direct impact on cancer cells’ response to treatment. Understanding these alterations is vital as they significantly influence the efficacy of chemotherapy. For instance, the modified ECM composition can create physical barriers that hinder drug penetration, reducing the effectiveness of chemotherapy within the tumor. Moreover, alterations in the ECM-associated signaling pathways can activate resistance mechanisms in cancer cells, allowing them to evade the cytotoxic effects of chemotherapy agents.

Exploring cancer cell responses in this altered post-chemotherapy ECM environment is crucial. Cancer cells adapt to the new biomechanical and biochemical cues of the ECM, exhibiting changes in behavior, migration, and survival mechanisms. These adaptive responses often lead to a decreased sensitivity of cancer cells to chemotherapy, resulting in treatment resistance and disease progression.

Researchers are investigating therapeutic strategies targeting ECM remodeling and associated signaling pathways to combat this challenge as potential avenues to overcome chemoresistance. Clinical trials are underway, exploring various agents and approaches to modulate the tumor microenvironment to enhance chemotherapy effectiveness and mitigate treatment resistance in cancer patients. Understanding and targeting these intricate interactions between chemotherapy, ECM remodeling, and cancer cell responses hold promise for advancing cancer treatment strategies.

Source: sciencedirect.com/science/article/abs/pii/S0304383523005347