Brain Cancer : Would you share what we know about the signaling cascades for glioblastoma and what this means for targeted treatments?

Would you share what we know about the signaling cascades for glioblastoma and what this means for targeted treatments?

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MarkGilbertMD (Physician - Neuro-Oncology (Verified) ) - 07 / 23 / 2012

Glioblastoma is a very complicated and heterogeneous disease. Even individual tumors may have tumor cells with very different characteristics, most notably the signaling cascades. These signaling cascades are an important component of normal cell function and are important in maintaining the integrity of our varied organs. However, in the case of cancer such as glioblastoma, many of these signaling cascades are functioning abnormally and do not maintain the normal controls. For example, p53 is involved in the signaling pathway that is responsible for programmed cell death, an important normal function that allows old cells to be replaced by new cells. In many gliomas, the p53 gene has a mutation that reduces or loses its function so that these tumor cells do not have the mechanism to respond to injury by undergoing programmed death (apoptosis). This is only one example of a mutation that results in abnormal pathway function. There are many other mutations causing abnormal signaling cascade function such as isocitrate dehydrogenase 1 (IDH1) involved in energy production, epidermal growth factor receptor (EGFR) resulting in abnormal tumor cell proliferation and resistance to death, and a variety of mutations in other cascades leading to abnormal function. Additionally, some cascades function abnormally as a result of over expression of genes, rather than a mutation of a gene. Examples include EGFR as well as the platelet derived growth factor receptor (PDGFR) and others. Each individual glioblastoma tumor can be characterized by having multiple abnormalities in the signaling cascades, thereby making it challenging to find the most important ones to target with treatment.

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