TY - JOUR
T1 - Protein kinase inhibitors for the treatment of prostate cancer
AU - Chau, Vincent
AU - Madan, Ravi A.
AU - Aragon-Ching, Jeanny B.
N1 - Funding Information:
This manuscript has not been funded.
Publisher Copyright:
© 2021 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
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U2 - 10.1080/14656566.2021.1925250
DO - 10.1080/14656566.2021.1925250
M3 - Review article
C2 - 33989112
AN - SCOPUS:85106033558
VL - 22
SP - 1889
EP - 1899
JO - Expert Opinion on Pharmacotherapy
JF - Expert Opinion on Pharmacotherapy
SN - 1465-6566
IS - 14
ER -