TGFß in Pancreas and Colorectal Cancer: Opportunities to Overcome Therapeutic Resistance.

ABSTRACT

TGFß is a pleiotropic signaling pathway that plays a pivotal role in regulating a multitude of cellular functions. TGFß has a dual role in cell regulation where it induces growth inhibition and cell death; however, it can switch to a growth-promoting state under cancerous conditions. TGFß is upregulated in colorectal cancer and pancreatic cancer, altering the tumor microenvironment and immune system and promoting a mesenchymal state. The upregulation of TGFß in certain cancers leads to resistance to immunotherapy, and attempts to inhibit TGFß expression have led to reduced therapeutic resistance when combined with chemotherapy and immunotherapy. Here, we review the current TGFß inhibitor drugs in clinical trials for pancreatic and colorectal cancer, with the goal of uncovering advances in improving clinical efficacy for TGFß combinational treatments in patients. Furthermore, we discuss the relevance of alterations in TGFß signaling and germline variants in the context of personalizing treatment for patients who show lack of response to current therapeutics.