More than a Decade of Tyrosine Kinase Inhibitors in the Treatment of Solid Tumors: What We Have Learned and What the Future Holds

Abstract

The use of tyrosine kinase inhibitors (TKIs) in the treatment of solid tumors is the expected standard of care for many types of tumors. Since the description of signal transduction pathways, followed by the development of small molecules designed to inhibit those pathways, there has been significant improvement not only in progression-free survival and overall survival but also in aiming toward chemotherapy-free treatment of solid tumors to maximize quality of life. This article reviews available TKIs and discusses toxicity, dosing, and resistance.

Keywords: EGFR mutation; TKI toxicities; TKIs; signaling pathways; solid tumors; targeted therapy; tyrosine kinase inhibitors.

Figure 1

Patient with relapse of GIST tumor with peritoneal, adrenal, and hepatic metastasis (left images) 2 years after individual discontinuation of imatinib shows partial response after reexposure to imatinib 400 mg daily. Measurable response was shown in the liver (34.82 mm before and 29 mm after) and the left adrenal gland (40.13 mm before and 30.64 mm after). Peritoneal metastasis with thickening of the peritoneum is visible on the lower left image, showing regress on the lower right image.

Figure 2

Impaired wound healing after gluteal abscess under pazopanib and later axitinib treatment for metastatic renal cell cancer. Osteosynthesis material of the hip after surgery for fracture because metastasis is visible.