TY - JOUR
T1 - Role of the GH-IGF1 system in progression of cancer
AU - Werner, Haim
AU - Laron, Zvi
N1 - Publisher Copyright:
© 2020 Elsevier B.V.
PY - 2020/12/1
Y1 - 2020/12/1
N2 - Emerging evidence links the growth hormone (GH)-insulin-like growth factor-1 (IGF1) endocrine axis to cancer development. While this putative correlation is of major translational relevance, most clinical and epidemiological reports to date found no causal linkage between GH therapy and enhanced cancer risk. Thus, it is generally agreed that GH therapy constitutes a safe pharmacological intervention. The present review focuses on a number of issues in the area of GH-IGF1 action in cancer development. Emphasis is given to the idea that GH and IGF1 do not conform to the definition of oncogenic factors. Specifically, these hormones, even at high pharmacological doses, are unable to induce malignant transformation. However, the GH-IGF1 axis is capable of ‘pushing’ already transformed cells through the various phases of the cell cycle. Viral and cellular oncogenes require an intact IGF1 signaling pathway in order to elicit transformation; in other words, oncogenic agents adopt the IGF1 pathway. This universal mechanism of action of oncogenes has broad implications in oncology. Our review provides an in-depth analysis of the interplay between the GH-IGF1 axis and cancer genes, including tumor suppressors p53 and BRCA1. Finally, the safety of GH therapy in both children and adults needs further long-term follow-up studies.
AB - Emerging evidence links the growth hormone (GH)-insulin-like growth factor-1 (IGF1) endocrine axis to cancer development. While this putative correlation is of major translational relevance, most clinical and epidemiological reports to date found no causal linkage between GH therapy and enhanced cancer risk. Thus, it is generally agreed that GH therapy constitutes a safe pharmacological intervention. The present review focuses on a number of issues in the area of GH-IGF1 action in cancer development. Emphasis is given to the idea that GH and IGF1 do not conform to the definition of oncogenic factors. Specifically, these hormones, even at high pharmacological doses, are unable to induce malignant transformation. However, the GH-IGF1 axis is capable of ‘pushing’ already transformed cells through the various phases of the cell cycle. Viral and cellular oncogenes require an intact IGF1 signaling pathway in order to elicit transformation; in other words, oncogenic agents adopt the IGF1 pathway. This universal mechanism of action of oncogenes has broad implications in oncology. Our review provides an in-depth analysis of the interplay between the GH-IGF1 axis and cancer genes, including tumor suppressors p53 and BRCA1. Finally, the safety of GH therapy in both children and adults needs further long-term follow-up studies.
KW - Growth hormone (GH)
KW - IGF1 receptor
KW - Insulin-like growth factor-1 (IGF1)
KW - Laron syndrome
KW - Mechanisms of cancer protection
UR - http://www.scopus.com/inward/record.url?scp=85090733190&partnerID=8YFLogxK
U2 - 10.1016/j.mce.2020.111003
DO - 10.1016/j.mce.2020.111003
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C2 - 32919021
AN - SCOPUS:85090733190
SN - 0303-7207
VL - 518
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
M1 - 111003
ER -