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Genes Dis. 2015 Mar 1;2(1):13-25.

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

Author information

1
The University of Chicago Pritzker School of Medicine, Chicago, IL 60637, USA ; Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, 5841 South Maryland Avenue, MC 3079, Chicago, IL 60637, USA.
2
Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, 5841 South Maryland Avenue, MC 3079, Chicago, IL 60637, USA ; Ministry of Education Key Laboratory of Diagnostic Medicine, The Affiliated Hospitals of Chongqing Medical University, Chongqing 400016, China.
3
Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, 5841 South Maryland Avenue, MC 3079, Chicago, IL 60637, USA ; Department of Orthopaedic Surgery, Xiang-Ya Hospital of Central South University, Changsha 410008, China.
4
Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, 5841 South Maryland Avenue, MC 3079, Chicago, IL 60637, USA ; School of Bioengineering, Chongqing University, Chongqing, China.
5
Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, 5841 South Maryland Avenue, MC 3079, Chicago, IL 60637, USA ; Department of Orthopaedic Surgery, the Second Affiliated Hospital of Lanzhou University, Lanzhou, Gansu 730000, China.
6
Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, 5841 South Maryland Avenue, MC 3079, Chicago, IL 60637, USA.

Abstract

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.

KEYWORDS:

Cancer; Insulin-like growth factor; Resistance; Therapy; Tumorigenesis

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