TY - JOUR
T1 - Investigational IGF1R inhibitors in early stage clinical trials for cancer therapy
AU - Werner, Haim
AU - Sarfstein, Rive
AU - Bruchim, Ilan
N1 - Publisher Copyright:
© 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2019/12/2
Y1 - 2019/12/2
N2 - Introduction: The insulin-like growth factors (IGFs) are a family of secreted peptide hormones with important roles in different cellular and organism functions. The biological activities of the IGFs are mediated by the IGF1 receptor (IGF1R), a cell surface, tyrosine kinase-containing heterotetramer that is linked to numerous cytoplasmic signaling cascades. The IGF1R displays potent antiapoptotic, pro-survival capacities and plays a key role in malignant transformation. Research has identified the IGF1R as a candidate therapeutic target in cancer. Areas covered: We offer a synopsis of ongoing efforts to target the IGF axis for therapeutic purposes. Our review includes a digest of early experimental work that led to the identification of IGF1R as a candidate therapeutic target in oncology. Expert opinion: Targeting of the IGF axis has yielded disappointing results in phase III trials, but it is important to learn from this to improve future trials in a rational manner. The potential of anti-IGF1R antibodies and small molecular weight inhibitors, alone or in combination with chemotherapy or other biological agents, should be investigated further in randomized studies. Moreover, the implementation of predictive biomarkers for patient selection will improve the outcome of future trials. Emerging personalized medicine could have a major impact on IGF1R targeting.
AB - Introduction: The insulin-like growth factors (IGFs) are a family of secreted peptide hormones with important roles in different cellular and organism functions. The biological activities of the IGFs are mediated by the IGF1 receptor (IGF1R), a cell surface, tyrosine kinase-containing heterotetramer that is linked to numerous cytoplasmic signaling cascades. The IGF1R displays potent antiapoptotic, pro-survival capacities and plays a key role in malignant transformation. Research has identified the IGF1R as a candidate therapeutic target in cancer. Areas covered: We offer a synopsis of ongoing efforts to target the IGF axis for therapeutic purposes. Our review includes a digest of early experimental work that led to the identification of IGF1R as a candidate therapeutic target in oncology. Expert opinion: Targeting of the IGF axis has yielded disappointing results in phase III trials, but it is important to learn from this to improve future trials in a rational manner. The potential of anti-IGF1R antibodies and small molecular weight inhibitors, alone or in combination with chemotherapy or other biological agents, should be investigated further in randomized studies. Moreover, the implementation of predictive biomarkers for patient selection will improve the outcome of future trials. Emerging personalized medicine could have a major impact on IGF1R targeting.
KW - IGF1 receptor (IGF1R)
KW - Insulin-like growth factor-1 (IGF1)
KW - cancer
KW - targeted therapy
UR - http://www.scopus.com/inward/record.url?scp=85075404422&partnerID=8YFLogxK
U2 - 10.1080/13543784.2019.1694660
DO - 10.1080/13543784.2019.1694660
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.systematicreview???
AN - SCOPUS:85075404422
SN - 1354-3784
VL - 28
SP - 1101
EP - 1112
JO - Expert Opinion on Investigational Drugs
JF - Expert Opinion on Investigational Drugs
IS - 12
ER -