Protein kinase inhibitors for the treatment of prostate cancer

Introduction: Protein kinases have emerged as targetable pathways used in metastatic prostate cancer given their role in prostatic tumor growth, proliferation and metastases. Protein kinase inhibitors are small molecules that target varying pathways including the breakpoint cluster region (BCR)-Abelson tyrosine kinase (ABL), colony stimulating factor-1 receptor (CSF1R), vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) and phosphoinositide 3-kinase (PI3K) pathways and have been studied in prostate cancer trials with variable results. In particular, cabozantinib when used in combination trials and ipatasertib, when used with abiraterone in patients who harbor phosphatase and tensin homologue (PTEN) loss, have been promising. Areas Covered: This article reviews the key early and late phase clinical trials currently investigating the use of protein kinase inhibitors in prostate cancer. Expert opinion: While multiple kinase inhibitors show promising results in prostate cancer, none have yet garnered Food and Drug Administration (FDA) approval. Studies are ongoing with the best candidate drugs discussed herein. However, multiple drugs have failed primary endpoints in prostate cancer. Therefore, further understanding of the potential mechanisms of resistance, combination and trial design of combination therapy may help pave the way for targeting kinase inhibition in prostate cancer.