Oncogenomic and Proteomics Lab, Department of Pathology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298-0662, USA.
Recent Pat Anticancer Drug Discov. 2011 May;6(2):166-77. doi: 10.2174/157489211795328512.
The IGF system plays a major role in growth, development and maintenance of homeostasis in normal cells and also contributes towards proliferation of malignant cells. Any disruption in the IGF system has its implications on growth retardation, atherosclerosis, insulin resistance and cancer. Imbalances in the IGF axis are known to contribute towards the progression of breast cancer. Due to the ubiquitous nature of the components of the IGF system, targeting specific members of the axis has gained attention over the past decades. The most elaborately investigated component as a therapeutic target in the system is the IGF-IR and studies have been pursued to inhibit IGF-IR by the administration of monoclonal antibodies and tyrosine kinase inhibitors. Very recently, a novel cell death receptor that binds specifically to IGFBP-3 was identified. It has also been shown that the IGFBP-3/IGFBP-3 receptor may be impaired in breast and prostate cancer. In this review, we present the mechanisms used to target the IGF system in various diseased states, emphasizing on breast cancer. We further discuss currently available therapeutic approaches and summarize the latest patents published in the field of IGF-I/IGF-IR and IGFBP-3/IGFBP-3R systems.
IGF 系统在正常细胞的生长、发育和维持内稳态方面发挥着重要作用，也有助于恶性细胞的增殖。IGF 系统的任何失调都会导致生长迟缓、动脉粥样硬化、胰岛素抵抗和癌症。已知 IGF 轴的失衡会导致乳腺癌的进展。由于 IGF 系统的各个组成部分无处不在，因此过去几十年来，靶向该轴的特定成员已成为关注焦点。作为该系统中治疗靶点的最详细研究的成分是 IGF-IR，并且已经进行了研究以通过施用单克隆抗体和酪氨酸激酶抑制剂来抑制 IGF-IR。最近，鉴定出一种专门结合 IGFBP-3 的新型细胞死亡受体。也已经表明，IGFBP-3/IGFBP-3 受体在乳腺癌和前列腺癌中可能受损。在这篇综述中，我们介绍了在各种疾病状态下靶向 IGF 系统的机制，重点介绍了乳腺癌。我们进一步讨论了目前可用的治疗方法，并总结了 IGF-I/IGF-IR 和 IGFBP-3/IGFBP-3R 系统领域的最新专利。
