Targeting the IGF-Axis for Cancer Therapy: Development and Validation of an IGF-Trap as a Potential Drug.
IGF-I receptor
IGF-Trap
signaling
targeted therapeutics
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
29 04 2020
29 04 2020
Historique:
received:
01
04
2020
revised:
22
04
2020
accepted:
23
04
2020
entrez:
6
5
2020
pubmed:
6
5
2020
medline:
30
3
2021
Statut:
epublish
Résumé
The insulin-like growth factor (IGF)-axis was implicated in cancer progression and identified as a clinically important therapeutic target. Several IGF-I receptor (IGF-IR) targeting drugs including humanized monoclonal antibodies have advanced to phase II/III clinical trials, but to date, have not progressed to clinical use, due, at least in part, to interference with insulin receptor signaling and compensatory signaling by the insulin receptor (IR) isoform A that can bind IGF-II and initiate mitogenic signaling. Here we briefly review the current state of IGF-targeting biologicals, discuss some factors that may be responsible for their poor performance in the clinic and outline the stepwise bioengineering and validation of an IGF-Trap-a novel anti-cancer therapeutic that could bypass these limitations. The IGF-Trap is a heterotetramer, consisting of the entire extracellular domain of the IGF-IR fused to the Fc portion of human IgG
Identifiants
pubmed: 32365498
pii: cells9051098
doi: 10.3390/cells9051098
pmc: PMC7290707
pii:
doi:
Substances chimiques
Antibodies, Monoclonal
0
IGF1 protein, human
0
IGF1R protein, human
0
Pharmaceutical Preparations
0
Insulin-Like Growth Factor I
67763-96-6
Receptor, IGF Type 1
EC 2.7.10.1
Receptor, Insulin
EC 2.7.10.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : CIHR
ID : MOP-77677
Pays : Canada
Organisme : CIHR
ID : PP2-141724
Pays : Canada
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