From TGF-β to Cancer Therapy

Xuemei      Huang; Chung      Lee

doi:10.2174/1389450033491181

Abstract

This article will introduce a novel concept in the use of TGF-β insensitive host immune cells in cancer therapy. TGF-β is a multi-functional cytokine. At a cellular level, it mediates cellular proliferation, growth arrest, differentiation and apoptosis. Because of the above cellular effects, TGF-β is able to regulate a host of patho-physiological events in vivo , such as normal embryonic development, angiogenesis in tumor tissues, malignant transformation and immune surveillance. As a general rule, its direct effect on cancer cells is inhibition to cancer growth. However cancer cells are able to acquire the ability to evade this inhibitory effect of TGF-β by becoming insensitive to TGF-β. Furthermore, these malignant cells are able to produce large quantities of TGF-β. The consequence of over expression of TGF-β by cancer cells is an important factor for subsequent tumor progression. The excess amount of TGF-β promotes tumor angiogenesis and immune suppression. The latter effect of TGF-β is the most devastating to the host. The present discussion is focused on the role of TGF-β insensitive immune cells in cancer growth. The host immune system offers a natural defense program against cancer. But, this natural immune surveillance is rendered ineffective by an overproduction of TGF-β derived from the tumor cells. Rendering the host immune cells insensitive to TGF-β in a gene therapy program offers a hope for us to successfully combat against cancer. Based on the above discussion, it is encouraging that there is a possibility for us to achieve a cure in cancer using TGF-β insensitive immune cells in gene therapy.

Keywords: transforming growth factor-beta, cancer therapy, receptors, insensitive immune cells, serine/threonine kinases, Cycline-dependent kinases (cdks),, myc family members, smads family