TY - JOUR
T1 - Early drug development of inhibitors of the insulin-like growth factor-I receptor pathway
T2 - Lessons from the first clinical trials
AU - Rodon, Jordi
AU - DeSantos, Victoria
AU - Ferry, Robert Jean
AU - Kurzrock, Razelle
PY - 2008
Y1 - 2008
N2 - The insulin-like growth factor-I receptor (IGF-IR) was first cloned in 1986. Since then, intense work has defined classic phosphorelays activated via the IGF-IR, which regulate cell proliferation, apoptosis, motility, and fate. The understanding of the roles of hormones in cancer and the growth hormone-IGF-IGF-binding protein axis specifically has yield to a second wave of development: the design of specific inhibitors that interrupt the signaling associated with this axis. The ability to manipulate these pathways holds not only significant therapeutic implications but also increase the chance of deeper insight about the role of the axis in carcinogenesis and metastasis. Nowadays, >25 molecules with the same goal are at different stages of development. Here, we review the clinical and preclinical experience with the two most-investigated strategies, tyrosine kinase inhibitors and monoclonal antibodies, and the advantages and disadvantages of each strategy, as well as other alternatives and possible drug combinations. We also review the biomarkers explored in the first clinical trials, the strategies that have been explored thus far, and the clinical trials that are going to explore their role in cancer treatment.
AB - The insulin-like growth factor-I receptor (IGF-IR) was first cloned in 1986. Since then, intense work has defined classic phosphorelays activated via the IGF-IR, which regulate cell proliferation, apoptosis, motility, and fate. The understanding of the roles of hormones in cancer and the growth hormone-IGF-IGF-binding protein axis specifically has yield to a second wave of development: the design of specific inhibitors that interrupt the signaling associated with this axis. The ability to manipulate these pathways holds not only significant therapeutic implications but also increase the chance of deeper insight about the role of the axis in carcinogenesis and metastasis. Nowadays, >25 molecules with the same goal are at different stages of development. Here, we review the clinical and preclinical experience with the two most-investigated strategies, tyrosine kinase inhibitors and monoclonal antibodies, and the advantages and disadvantages of each strategy, as well as other alternatives and possible drug combinations. We also review the biomarkers explored in the first clinical trials, the strategies that have been explored thus far, and the clinical trials that are going to explore their role in cancer treatment.
UR - http://www.scopus.com/inward/record.url?scp=54049108939&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=54049108939&partnerID=8YFLogxK
U2 - 10.1158/1535-7163.MCT-08-0265
DO - 10.1158/1535-7163.MCT-08-0265
M3 - Review article
C2 - 18790742
AN - SCOPUS:54049108939
SN - 1535-7163
VL - 7
SP - 2575
EP - 2588
JO - Molecular cancer therapeutics
JF - Molecular cancer therapeutics
IS - 9
ER -