Research Topic

The role of the Insulin/IGFs system in cancer: critical points in dysregulation, targeting problems and new blocking strategies

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It is well established that dysregulation of several components of the insulin/IGF system are involved in cancer and sustain cancer progression. Disturbances in the insulin/IGF system may regard alterations of circulating levels of insulin and/or IGFs and of systemic production of IGF binding proteins ...

It is well established that dysregulation of several components of the insulin/IGF system are involved in cancer and sustain cancer progression. Disturbances in the insulin/IGF system may regard alterations of circulating levels of insulin and/or IGFs and of systemic production of IGF binding proteins (IGF-BPs) as well as the overexpression of receptors, and autocrine/paracrine production of growth factors by cancer cells.
This extensive knowledge has been translated in cancer therapy mainly by approaches aiming to target the IGF-IR, on the basis of its prominent involvement in growth regulation and the scarce contribution to glucose metabolism. However, in humans, IGF-IR targeting has resulted of limited efficacy. Mechanisms of resistance are still poorly understood, but include the involvement of other receptors of the system, such as the insulin receptor A (IR-A) and IR-A/IGF-IR hybrids, which may substitute for the lack of IGF-IR, and/or induce clonal selection. Resistance to anti-IGF-IR treatment may also come from the extensive crosstalk between Insulin/IGF system with other pathways involved in cancer progression, such as those involved in cell stemness and epithelial-mesenchymal transition (EMT), as well as with pathways activated by sex steroid hormones or other peptide growth factors. At the same time, newly identified mechanisms involved in IGF-IR signaling and trafficking regulation, may also play a role in cancer resistance.
A better understanding of the mechanisms involved in cancer resistance to IGF-IR blockade will allow the design of more efficacious therapeutical approaches.


We welcome original as well as review articles on a broad range of topics related to the malignancies related to the dysregulation of the Insulin/IGFs axis, which may include epidemiology, mechanistic studies, animal models, potential strategies of prevention and treatment.
Potential topics include, but are not limited to:
1. Epidemiological and mechanistic studies focusing on genetic, epigenetic or environmental factors associated with dysregulation of the insulin/IGF axis.
2. Possible role of endocrine disruptors.
3. The potential of critical alterations of the insulin/IGF system on specific aspects of cancer.
4. Efficacy and side effects of existing IGF-IR blocking therapies.
5. New potential targets of the insulin/IGF system.
6. Preclinical or clinical studies with new agents inhibiting critical components/pathways of the insulin/IGF system.
7. Possible role of dietetic regimens, nutraceutics or life style changes in normalizing alterations of the insulin/IGF axis relevant to cancer.
8. The potential of biomarkers in IGF system target therapies.


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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