Title:Designing Novel Therapies Against Sarcomas in the Era of Personalized Medicine and Economic Crisis
Volume: 19
Issue: 30
Author(s): Maria Cristina Manara, Cecilia Garofalo, Stefano Ferrari, Antonino Belfiore and Katia Scotlandi
Affiliation:
Keywords:
Sarcomas, insulin-like growth factor (IGF) system, metformin, targeted therapies, rare diseases.
Abstract: Drug “repurposing” is the process of finding new therapeutic indications for existing drugs, and can be considered as a more
efficient and realistic strategy for the design of therapies against rare diseases than the current efforts to develop targeted-drugs. In this
review, we explore the difficulties related to the identification and development of tailored therapies for individual patients with sarcomas,
which are relatively rare diseases characterized by an extreme genetic and histologic variability. Overall, sarcomas comprise about
1% of all adult tumors and 10% of pediatric cancers. They are conventionally divided in bone and soft-tissue sarcomas, considering their
site of origin. However, each group is highly heterogeneous and recent global characterization of their genetic alterations has clearly
identified the existence of peculiarities that render these group of tumors even more “orphan” for pharmaceutical companies to develop
and market specific- targeted drugs. The present review highlights key examples of molecular targets identification in bone sarcomas, reexamining
the history of insulin-like growth factor receptor (IGF-IR) and its role in physiology and in cancer as well as developments regarding
phase I to II clinical trials of agents directed against this receptor. The IGF system is quite complex, with many players in the
field. Insulin receptor function in cancer cells has certainly been underestimated, but also little attention was paid to the type of ligands
that are mainly involved in each tumor type. Strategies considering the system in its complex are encouraged and, in this context, drugs
aimed at reducing circulating insulin levels, such as metformin, should receive attention as potential anti-cancer agents.
