The Role of IGF/IGF-IR-Signaling and Extracellular Matrix Effectors in Bone Sarcoma Pathogenesis

Cancers

Monica Neagu¹  Kyoko Hida²  GeorgeN. Tzanakakis³  Ioanna Spyridaki³  Aikaterini Berdiaki³  Dragana Nikitovic³  Eirini-Maria Giatagana³  AristidisM. Tsatsakis⁴ 

[1] Department of Immunology, Victor Babes National Institute of Pathology, 050096 Bucharest, Romania;Department of Vascular Biology and Molecular Pathology, Hokkaido University Graduate School of Dental Medicine, Sapporo 060-8586, Japan;Laboratory of Histology-Embryology, School of Medicine, University of Crete, 71003 Heraklion, Greece;Laboratory of Toxicology, School of Medicine, University of Crete, 71003 Heraklion, Greece;

关键词: bone sarcoma;    IGF signaling;    IGF-1R;    extracellular matrix;    tumor microenvironment;    cancer therapy;   

DOI  :  10.3390/cancers13102478

来源: DOAJ

【 摘 要 】

Bone sarcomas, mesenchymal origin tumors, represent a substantial group of varying neoplasms of a distinct entity. Bone sarcoma patients show a limited response or do not respond to chemotherapy. Notably, developing efficient chemotherapy approaches, dealing with chemoresistance, and preventing metastasis pose unmet challenges in sarcoma therapy. Insulin-like growth factors 1 and 2 (IGF-1 and -2) and their respective receptors are a multifactorial system that significantly contributes to bone sarcoma pathogenesis. Whereas failures have been registered in creating novel targeted therapeutics aiming at the IGF pathway, new agent development should continue, evaluating combinatorial strategies for enhancing antitumor responses and better classifying the patients that could best benefit from these therapies. A plausible approach for developing a combinatorial strategy is to focus on the tumor microenvironment (TME) and processes executed therein. Herewith, we will discuss how the interplay between IGF-signaling and the TME constituents affects sarcomas’ basal functions and their response to therapy. This review highlights key studies focusing on IGF signaling in bone sarcomas, specifically studies underscoring novel properties that make this system an attractive therapeutic target and identifies new relationships that may be exploited. Potential direct and adjunct therapeutical implications of the extracellular matrix (ECM) effectors will also be summarized.

【 授权许可】

Unknown