Small-Molecule Protein Kinase Inhibitors and Their Effects on the Immune System: Implications for Cancer Treatment

Abstract

Oncogenic signaling pathways have emerged as key targets for the development of small-molecule inhibitors, with several protein kinase inhibitors already in clinical use for cancer patients. In addition to their role in tumorigenesis, many of the molecules and signaling pathways targeted by these inhibitors are also important in the signaling and interaction of immune cells, such as T cells and dendritic cells. Not surprisingly, there is increasing evidence that many of these inhibitors can have a substantial impact on immune function, both stimulating and downregulating an immune response. In order to illustrate the important role of signaling molecule inhibition in the modulation of immune function, we will discuss the exemplary pathways MAPK, AKT–PI3K–mTOR and VEGF–VEGFR, as well as selected small-molecule inhibitors, whose impact on immune cells has been studied more extensively.

KEYWORDS::

• cancer
• immunotherapy
• MAPK
• PI3K–AKT–mTOR
• VEGF–VEGFR tyrosine kinase inhibitor

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.