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.
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.