In Situ Drug Delivery to Breast Cancer-Associated Extracellular Matrix

The extracellular matrix (ECM) contributes to tumor progression through changes induced by tumor and stromal cell signals that promote increased ECM density and stiffness. The increase in ECM stiffness is known to promote tumor cell invasion into surrounding tissues and metastasis. In addition, this scar like ECM creates a protective barrier around the tumor that reduces the effectiveness of innate and synthetic antitumor agents. Herein, clinically approved breast cancer therapies as well as novel experimental approaches that target the ECM are discussed, including in situ hydrogel drug delivery systems, an emerging technology the delivers toxic chemotherapeutics, gene-silencing microRNAs, and tumor suppressing immune cells directly inside the tumor. Intratumor delivery of therapeutic agents has the potential to drastically reduce systemic side effects experienced by the patient and increase the efficacy of these agents. This review also describes the opposing effects of ECM degradation on tumor progression, where some studies report improved drug delivery and delayed cancer progression and others report enhanced metastasis and decreased patient survival. Given the recent increase in ECM-targeting drugs entering preclinical and clinical trials, understanding and addressing the factors that impact the effect of the ECM on tumor progression is imperative for the sake of patient safety and survival outcome.