Insulin-Like Growth Factor Signaling in Cancer Biology

The insulin-like growth factor (IGF) signalling axis is fundamental to normal development and is frequently co-opted in malignancies, including breast, colorectal and prostate cancers. Binding of IGF-1 and IGF-2 to the type 1 IGF receptor (IGF-1R), a receptor tyrosine kinase, triggers downstream PI3K/AKT and MAPK cascades that drive proliferation, survival, motility and angiogenesis. Dysregulation may arise from ligand or receptor overexpression, loss of IGF binding proteins (IGFBPs) that sequester ligands, or alternative splicing of the insulin receptor (IR) into mitogenic IR-A and metabolic IR-B isoforms. Aberrant IGF signalling underpins tumour initiation, progression and resistance to chemotherapy, endocrine agents and targeted therapies. Cross-talk with oestrogen receptor pathways, metabolic cues and the tumour microenvironment further complicates therapeutic interception. Initial clinical trials of IGF-1R inhibitors were limited by toxicities, lack of predictive biomarkers and adaptive resistance. Contemporary research is refining patient stratification, exploring combination regimens and harnessing the immunomodulatory functions of the IGF axis. Given the global rise in obesity-associated cancers, a deeper understanding of IGF signalling in metabolic and inflammatory contexts is critical for effective translation into clinical practice.

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Insulin-Like Growth Factor Signaling in Cancer Biology publication trend

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Technical terms

Insulin-like growth factor (IGF): Peptide hormones (IGF-1, IGF-2) that regulate cell proliferation, differentiation and survival.

IGF-1 receptor (IGF-1R): A receptor tyrosine kinase that transduces signals from IGF ligands via autophosphorylation and activation of downstream effectors.

IGF binding proteins (IGFBPs): A family of proteins that bind IGF ligands, modulating their bioavailability and receptor engagement.

Receptor tyrosine kinase (RTK): A cell-surface receptor class that initiates signalling through tyrosine phosphorylation following ligand binding.

Tumour microenvironment (TME): The surrounding stromal, immune and vascular components that interact dynamically with tumour cells.

Alternative splicing: The process by which different exon combinations generate multiple mRNA transcripts—and thus protein isoforms—from a single gene.

References

1. IGF-1R targeting in cancer – does sub-cellular localization matter?. Journal of Experimental & Clinical Cancer Research (2023).
2. Manipulating the tumor immune microenvironment to improve cancer immunotherapy: IGF1R, a promising target. Frontiers in Immunology (2024).
3. Insulin receptor alternative splicing in breast and prostate cancer. Cancer Cell International (2024).
4. Insulin-like growth factor receptor signaling in tumorigenesis and drug resistance: a challenge for cancer therapy. Journal of Hematology & Oncology (2020).