The anti-metastasis effect of low-dose carbon monoxide

Abstract

: Metastasis is the primary cause of cancer-related deaths. Because of the anatomically diffused localizations in different organs, treating metastatic cancer with conventional surgery or radiotherapy is challenging. Systemic therapies, including chemotherapy, immunotherapy, and targeted therapy, are used for metastatic cancer treatment. However, resistance to chemotherapy often develops over time, and immunotherapy or targeted therapy is not available for every cancer type. Improved systemic therapies for metastatic cancer are urgently needed. Among all forms of cancer, pancreatic ductal adenocarcinoma (PDAC) is a lethal type due to the following characteristics: early distant metastasis, abundant desmoplastic stroma, insufficient therapeutics, and frequent chemoresistance. Carbon monoxide (CO) is produced endogenously in humans and has been established as an important, biologically active signaling molecule. Accumulating evidence suggests the therapeutic applications of safe, low-dose CO for various diseases. Recently, low-dose CO was shown to suppress metastasis of PDAC in an orthotopic mouse model of liver metastasis and a spontaneous PDAC metastasis mouse model after the removal of primary tumor xenograft tumors. In this mini-review, we discuss the findings and the potential development of CO-based systemic therapies for metastatic cancer. Specifically, many non-inhalation CO delivery modalities with easy control of dosages have been developed and can be further studied for their anti-metastatic properties.