+1 Recommend
1 collections
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Insulin-like growth factor (IGF) signaling in tumorigenesis and the development of cancer drug resistance


      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.


          One of the greatest obstacles to current cancer treatment efforts is the development of drug resistance by tumors. Despite recent advances in diagnostic practices and surgical interventions, many neoplasms demonstrate poor response to adjuvant or neoadjuvant radiation and chemotherapy. As a result, the prognosis for many patients afflicted with these aggressive cancers remains bleak. The insulin-like growth factor (IGF) signaling axis has been shown to play critical role in the development and progression of various tumors. Many basic science and translational studies have shown that IGF pathway modulators can have promising effects when used to treat various malignancies. There also exists a substantial body of recent evidence implicating IGF signaling dysregulation in the dwindling response of tumors to current standard-of-care therapy. By better understanding both the IGF-dependent and -independent mechanisms by which pathway members can influence drug sensitivity, we can eventually aim to use modulators of IGF signaling to augment the effects of current therapy. This review summarizes and synthesizes numerous recent investigations looking at the role of the IGF pathway in drug resistance. We offer a brief overview of IGF signaling and its general role in neoplasia, and then delve into detail about the many types of human cancer that have been shown to have IGF pathway involvement in resistance and/or sensitization to therapy. Ultimately, our hope is that such a compilation of evidence will compel investigators to carry out much needed studies looking at combination treatment with IGF signaling modulators to overcome current therapy resistance.

          Related collections

          Most cited references137

          • Record: found
          • Abstract: not found
          • Article: not found

          Insulin-like growth factors and neoplasia.

            • Record: found
            • Abstract: found
            • Article: not found

            Circulating concentrations of insulin-like growth factor-I and risk of breast cancer.

            Insulin-like growth factor (IGF)-I, a mitogenic and antiapoptotic peptide, can affect the proliferation of breast epithelial cells, and is thought to have a role in breast cancer. We hypothesised that high circulating IGF-I concentrations would be associated with an increased risk of breast cancer. We carried out a nested case-control study within the prospective Nurses' Health Study cohort. Plasma concentrations of IGF-I and IGF binding protein 3 (IGFBP-3) were measured in blood samples collected in 1989-90. We identified 397 women who had a diagnosis of breast cancer after this date and 620 age-matched controls. IGF-I concentrations were compared by logistic regression with adjustment for other breast-cancer risk factors. There was no association between IGF-I concentrations and breast-cancer risk among the whole study group. In postmenopausal women there was no association between IGF-I concentrations and breast-cancer risk (top vs bottom quintile of IGF-I, relative risk 0.85 [95% CI 0.53-1.39]). The relative risk of breast cancer among premenopausal women by IGF-I concentration (top vs bottom tertile) was 2.33 (1.06-5.16; p for trend 0.08). Among premenopausal women less than 50 years old at the time of blood collection, the relative risk was 4.58 (1.75-12.0; p for trend 0.02). After further adjustment for plasma IGFBP-3 concentrations these relative risks were 2.88 and 7.28, respectively. A positive relation between circulating IGF-I concentration and risk of breast cancer was found among premenopausal but not postmenopausal women. Plasma IGF-I concentrations may be useful in the identification of women at high risk of breast cancer and in the development of risk reduction strategies. Additional larger studies of this association among premenopausal women are needed to provide more precise estimates of effect.
              • Record: found
              • Abstract: found
              • Article: not found

              KRAS, Hedgehog, Wnt and the twisted developmental biology of pancreatic ductal adenocarcinoma.

              Pancreatic ductal adenocarcinoma (PDAC) is characterized by near-universal mutations in KRAS and frequent deregulation of crucial embryonic signalling pathways, including the Hedgehog (Hh) and Wnt-β-catenin cascades. The creation of mouse models that closely resemble the human disease has provided a platform to better understand when and in which cell types these pathways are misregulated during PDAC development. Here we examine the central part that KRAS plays in the biology of PDAC, and how the timing and location of Hh and Wnt-β-catenin signalling dictate the specification and oncogenic properties of PDAC.

                Author and article information

                Genes Dis
                Genes Dis
                Genes & Diseases
                31 December 2014
                15 November 2014
                1 March 2015
                14 May 2015
                : 2
                : 1
                : 13-25
                [a ] The University of Chicago Pritzker School of Medicine, Chicago, IL 60637, USA
                [b ] Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, 5841 South Maryland Avenue, MC 3079, Chicago, IL 60637, USA
                [c ] Ministry of Education Key Laboratory of Diagnostic Medicine, The Affiliated Hospitals of Chongqing Medical University, Chongqing 400016, China
                [d ] Department of Orthopaedic Surgery, Xiang-Ya Hospital of Central South University, Changsha 410008, China
                [e ] School of Bioengineering, Chongqing University, Chongqing, China
                [f ] Department of Orthopaedic Surgery, the Second Affiliated Hospital of Lanzhou University, Lanzhou, Gansu 730000, China
                Author notes
                [* ] Corresponding author. Tel.: +1 773 702 6216; fax: +1 773 702 4765. hluu@ 123456bsd.uchicago.edu (H.H. Luu). Peer review under responsibility of Chongqing Medical University.
                © 2014, Chongqing Medical University. Production and hosting by Elsevier B.V.

                This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/3.0/).


                cancer,insulin-like growth factor,resistance,therapy,tumorigenesis


                Comment on this article