The insulin and insulin-like growth factor receptor family in neoplasia: an update
Abstract
Although several early phase clinical trials raised enthusiasm for the use of insulin-like growth factor I receptor (IGF1R)-specific antibodies for cancer treatment, initial Phase III results in unselected patients have been disappointing. Further clinical studies may benefit from the use of predictive biomarkers to identify probable responders, the use of rational combination therapies and the consideration of alternative targeting strategies, such as ligand-specific antibodies and receptor-specific tyrosine kinase inhibitors. Targeting insulin and IGF signalling also needs to be considered in the broader context of the pathophysiology that relates obesity and diabetes to neoplasia, and the effects of anti-diabetic drugs, including metformin, on cancer risk and prognosis. The insulin and IGFI receptor family is also relevant to the development of PI3K-AKT pathway inhibitors.
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From Advances on immunotherapy for osteosarcoma (2024) · cites this paper as [124]
Cites
OWEN, M. R., DORAN, E., & HALESTRAP, A. P. (2000) · Biochemical Journal · doi:10.1042/bj3480607 · Cited by 2,157 · see citing works
Metformin is an AMP kinase-dependent growth inhibitor for breast cancer cells
Zakikhani, M., Dowling, R., Fantus, I. G., Sonenberg, N., & Pollak, M. (2006) · Cancer Research · doi:10.1158/0008-5472.can-06-1500 · Cited by 1,048 · see citing works
Self-citationKurtzhals, P., Schäffer, L., Sørensen, A., Kristensen, C., Jonassen, I., Schmid, C., & Trüb, T. (2000) · Diabetes · doi:10.2337/diabetes.49.6.999 · Cited by 739 · see citing works
Tanti, J.-F., & Jager, J. (2009) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2009.07.004 · Cited by 430 · see citing works
Metformin reduces endogenous reactive oxygen species and associated DNA damage
Algire, C., Moiseeva, O., Deschênes-Simard, X., Amrein, L., Petruccelli, L., Birman, E., Viollet, B., Ferbeyre, G., & Pollak, M. N. (2012) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-11-0536 · Cited by 372 · see citing works
Self-citationInsulin and its receptor: structure, function and evolution
De Meyts, P. (2004) · BioEssays · doi:10.1002/bies.20151 · Cited by 345 · see citing works
Metformin and Other Biguanides in Oncology: Advancing the Research Agenda
Pollak, M. (2010) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-10-0175 · Cited by 240 · see citing works
Self-citationUlanet, D. B., Ludwig, D. L., Kahn, C. R., & Hanahan, D. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0914076107 · Cited by 235 · see citing works
Metformin attenuates the stimulatory effect of a high-energy diet on in vivo LLC1 carcinoma growth
Algire, C., Zakikhani, M., Blouin, M.-J., Shuai, J. H., & Pollak, M. (2008) · Endocrine Related Cancer · doi:10.1677/erc-08-0038 · Cited by 185 · see citing works
Self-citation
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Cited by
Sorted by citations
Obesity and cancer risk: Emerging biological mechanisms and perspectives
Avgerinos, K. I., Spyrou, N., Mantzoros, C. S., & Dalamaga, M. (2019) · Metabolism · doi:10.1016/j.metabol.2018.11.001 · Cited by 1,567 · see citing works
Metformin: from mechanisms of action to therapies
Foretz, M., Guigas, B., Bertrand, L., Pollak, M., & Viollet, B. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.09.018 · Cited by 1,501 · see citing works
Self-citationThe hallmarks of cancer metabolism: still emerging
Pavlova, N. N., Zhu, J., & Thompson, C. B. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2022.01.007 · Cited by 1,418 · see citing works
Promoting Health and Longevity through Diet: From Model Organisms to Humans
Fontana, L., & Partridge, L. (2015) · Cell · doi:10.1016/j.cell.2015.02.020 · Cited by 1,245 · see citing works
Nutrients, foods, and colorectal cancer prevention
Song, M., Garrett, W. S., & Chan, A. T. (2015) · Gastroenterology · doi:10.1053/j.gastro.2014.12.035 · Cited by 700 · see citing works
Adiposity and cancer risk: new mechanistic insights from epidemiology
Renehan, A. G., Zwahlen, M., & Egger, M. (2015) · Nature Reviews Cancer · doi:10.1038/nrc3967 · Cited by 654 · see citing works
Fasting and cancer: molecular mechanisms and clinical application
Nencioni, A., Caffa, I., Cortellino, S., & Longo, V. D. (2018) · Nature Reviews Cancer · doi:10.1038/s41568-018-0061-0 · Cited by 518 · see citing works
Cancer cell survival during detachment from the ECM: multiple barriers to tumour progression
Buchheit, C. L., Weigel, K. J., & Schafer, Z. T. (2014) · Nature Reviews Cancer · doi:10.1038/nrc3789 · Cited by 367 · see citing works
Roles of oxidative stress in polycystic ovary syndrome and cancers
Zuo, T., Zhu, M., & Xu, W. (2016) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/8589318 · Cited by 319 · see citing works
Insulin–PI3K signalling: an evolutionarily insulated metabolic driver of cancer
Hopkins, B. D., Goncalves, M. D., & Cantley, L. C. (2020) · Nature Reviews Endocrinology · doi:10.1038/s41574-020-0329-9 · Cited by 288 · see citing works
Advances on immunotherapy for osteosarcoma
Yu, S., & Yao, X. (2024) · Molecular Cancer · doi:10.1186/s12943-024-02105-9 · Cited by 270 · see citing works
“The binding of ligand and IGF1R contributes to the proliferation, survival, transformation, metastasis, and angiogenesis [124].”
BackgroundInsulin resistance and cancer: The role of insulin and IGFs
Djiogue, S., Nwabo Kamdje, A. H., Vecchio, L., Kipanyula, M. J., Farahna, M., Aldebasi, Y., & Seke Etet, P. F. (2013) · Endocrine Related Cancer · doi:10.1530/erc-12-0324 · Cited by 263 · see citing works
Phenotypes of prediabetes and stratification of cardiometabolic risk
Stefan, N., Fritsche, A., Schick, F., & Häring, H.-U. (2016) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(16)00082-6 · Cited by 208 · see citing works
Targeting Cancer Metabolism: Dietary and Pharmacologic Interventions
Vernieri, C., Casola, S., Foiani, M., Pietrantonio, F., de Braud, F., & Longo, V. (2016) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-0615 · Cited by 202 · see citing works
Diabetes and Cancer: Risk, Challenges, Management and Outcomes
Shahid, R. K., Ahmed, S., Le, D., & Yadav, S. (2021) · Cancers · doi:10.3390/cancers13225735 · Cited by 187 · see citing works
Gérard, C., & Brown, K. A. (2018) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2017.09.014 · Cited by 136 · see citing works
Heilmann, A. M., Perera, R. M., Ecker, V., Nicolay, B. N., Bardeesy, N., Benes, C. H., & Dyson, N. J. (2014) · Cancer Research · doi:10.1158/0008-5472.can-13-2923 · Cited by 119 · see citing works
“phosphorylate IR substrate (IRS) proteins, which activate the PI3K–AKT–mTOR as well as the RAS-MAPK signaling axes (25), key effectors in oncogenic KRAS-driven PDAC develop-”
BackgroundIGF1R- and ROR1-Specific CAR T Cells as a Potential Therapy for High Risk Sarcomas
Huang, X., Park, H., Greene, J., Pao, J., Mulvey, E., Zhou, S. X., Albert, C. M., Moy, F., Sachdev, D., Yee, D., et al. (2015) · PLOS ONE · doi:10.1371/journal.pone.0133152 · Cited by 109 · see citing works
Sclafani, F., Kim, T. Y., Cunningham, D., Kim, T. W., Tabernero, J., Schmoll, H. J., Roh, J. K., Kim, S. Y., Park, Y. S., Guren, T. K., et al. (2015) · Journal of the National Cancer Institute · doi:10.1093/jnci/djv258 · Cited by 92 · see citing works
Nutrition and longevity—From mechanisms to uncertainties
Ekmekcioglu, C. (2020) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2019.1676698 · Cited by 87 · see citing works
Ferroni, P., Riondino, S., Buonomo, O., Palmirotta, R., Guadagni, F., & Roselli, M. (2015) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2015/183928 · Cited by 87 · see citing works
Obesity and Cancer: An Angiogenic and Inflammatory Link
Fukumura, D., Incio, J., Shankaraiah, R. C., & Jain, R. K. (2016) · Microcirculation · doi:10.1111/micc.12270 · Cited by 69 · see citing works
Development of covalent inhibitors: Principle, design, and application in cancer
Zheng, L., Li, Y., Wu, D., Xiao, H., Zheng, S., Wang, G., & Sun, Q. (2023) · MedComm – Oncology · doi:10.1002/mog2.56 · Cited by 71 · see citing works
The TGFβ pathway stimulates ovarian cancer cell proliferation by increasing IGF1R levels
Alsina‐Sanchis, E., Figueras, A., Lahiguera, Á., Vidal, A., Casanovas, O., Graupera, M., Villanueva, A., & Viñals, F. (2016) · International Journal of Cancer · doi:10.1002/ijc.30233 · Cited by 57 · see citing works
Molecular pathways: sensitivity and resistance to anti-EGFR antibodies
Bertotti, A., & Sassi, F. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-0848 · Cited by 45 · see citing works
Checkley, L. A., Rudolph, M. C., Wellberg, E. A., Giles, E. D., Wahdan-Alaswad, R. S., Houck, J. A., Edgerton, S. M., Thor, A. D., Schedin, P., Anderson, S. M., et al. (2017) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-16-0211-t · Cited by 43 · see citing works
Xin, W.-X., Fang, L., Fang, Q.-L., Zheng, X.-W., Ding, H.-Y., & Huang, P. (2018) · Medicine · doi:10.1097/md.0000000000010035 · Cited by 18 · see citing works
TRIB3-P62 interaction, diabetes and autophagy
Hua, F., & Hu, Z.-W. (2015) · Oncotarget · doi:10.18632/oncotarget.6108 · Cited by 9 · see citing works
- Authors
- Pollak, M.
- Venue
- Nature Reviews Cancer
- Published
- 2012-02-16
- Volume
- 12
- Issue
- 3
- Pages
- 159-169
- ISSN
- 1474-175X (ISSN-L)
- 1474-1768
- OpenAlex
- W2109600717
- Cited by
- 1,116
- References
- 9
- Citations by year
- 2026: 42 · 2025: 39 · 2024: 54 · 2023: 54 · 2022: 68 · 2021: 72 · 2020: 85 · 2019: 68 · 2018: 76 · 2017: 101 · 2016: 89 · 2015: 110 · 2014: 128 · 2013: 90 · 2012: 38
- FWCI
- 16.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature reviews. Cancer (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Keywords
- IGF-1 receptor, insulin signaling, IGF signalling, cancer therapy, predictive biomarkers, combination therapy, tyrosine kinase inhibitors, obesity and cancer, diabetes and cancer, metformin, PI3K/AKT inhibitors, cancer
- MeSH terms
- Animals, Clinical Trials as Topic, Multigene Family, Humans, Insulin, Insulin-Like Growth Factor I, Neoplasms, Signal Transduction, Receptors, Somatomedin
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