Background: Colorectal cancer (CRC) is one of the most common types of cancer and is associated
with an increasing rate of mortality. Transforming Growth Factor-Beta (TGF-β) is often upregulated in CRC, and
appears to play an important role in regulating cell proliferation, migration, immune surveillance, apoptosis, cell
differentiation, drug-resistance and many cellular processes that may be involved in CRC, and therefore underscores
its potential value as a therapeutic target in the treatment of CRC. An increased expression of the TGF-
β pathway has been associated with poor prognosis in several cancer types, including CRC.
Methods: Here, we describe the critical role of the TGF-β pathway in CRC as well as the preclinical and clinical
investigations on TGF-β inhibitors, with particular emphasis on recent findings with small-molecule inhibitors in
CRC. Several TGF-β inhibitors (e.g., Trabedersen, Galunisertib, Gradalis, PF-03446962, NIS793) have been
generated over the past decade for targeting this pathway.
Results: There is accumulating evidence of the therapeutic potential of this and other TGF-β inhibitors for the
treatment of other malignancies. These inhibitors might be used in combination with chemotherapy as well as
with other biological agents, in order to overcome different resistance mechanisms. However, further studies are
needed to identify determinants of the activity of TGF-β inhibitors, through the analysis of genetic and environmental
alterations affecting TGF-β and parallel pro-cancer pathways.
Conclusion: These studies will be critical to improving the efficacy and selectivity of current and future anticancer
strategies targeting TGF-β.