TGF‐β signaling in liver metastasis

• Published in: Clinical and translational medicine 2020-11, Vol.10 (7), p.e160-n/a
• Main Authors: Marvin, Dieuwke L, Heijboer, Rosan, ten Dijke, Peter, Ritsma, Laila
• Format: Article
• Language: English
• Subjects: cancer; immunotherapy; liver metastasis; Review; Reviews; targeted therapy; transforming growth factor beta; tumor microenvironment
• ISSN: 2001-1326; 2001-1326
• DOI: 10.1002/ctm2.160

The presence of liver metastases drastically worsens the prognosis of cancer patients. The liver is the second most prevalent metastatic site in cancer patients, but systemic therapeutic opportunities that target liver metastases are still limited. To aid the discovery of novel treatment options for metastatic liver disease, we provide insight into the cellular and molecular steps required for liver colonization. For successful colonization in the liver, adaptation of tumor cells and surrounding stroma is essential. This includes the formation of a pre‐metastatic niche, the creation of a fibrotic and immune suppressive environment, angiogenesis, and adaptation of tumor cells. We illustrate that transforming growth factor β (TGF‐β) is a central cytokine in all these processes. At last, we devise that future research should focus on TGF‐β inhibitory strategies, especially in combination with immunotherapy. This promising systemic treatment strategy has potential to eliminate distant metastases as the efficacy of immunotherapy will be enhanced. The liver is a permissive organ for metastasis, but adaptation of both liver environment and tumor cells is necessary for metastatic outgrowth. During liver metastasis formation, the cytokine TGF‐β promotes hepatic colonization by affecting the tumor cells, as well as tumor stroma, vasculature, and immune cells. Targeting TGF‐β, in combination with immunotherapy, has the potential to eliminate liver metastasis.