Cell Signal Mechanism To Provide New Therapeutic Cancer Target

Cell Signal Mechanism To Provide New Therapeutic Cancer Target
EGFR signaling (Image source)
Researchers have identified an important cell signaling mechanism that plays an important role in brain cancer and may provide a new therapeutic target. The findings were published in the journal Nature Communications.
Researchers found that this mechanism — a type of signaling termed constitutive or non-canonical epidermal growth factor receptor (EGFR) signaling — is highly active in glioblastomas, the most common type of adult brain cancer and a devastating disease with a poor prognosis. When activated in cancer cells, it protects the tumor cells, making them more resistant to chemotherapy treatment. The pathway may also have implications for other types of lung and breast cancers where overexpression of EGFR is a factor.
Glioblastomas (GBM) arise from astrocytes, which are star-shaped cells that make up the “glue-like” or supportive tissue of the brain, according to the American Brain Tumor Association. They represent about 17 percent of brain tumors, and are more common in males and those over 50.
Fueled by a good blood supply, they grow rapidly, increasing pressure on the brain and causing symptoms such as headaches, vomiting and nausea, speech and memory difficulties, muscle weakness on one side, and vision problems, depending on where the tumor grows in the brain. Due to that fast growth, average survival is just 15 months after diagnosis.
In their study, the researchers shed new light on why this difficult-to-treat cancer can be resistant to treatment. The epidermal growth factor receptor is frequently amplified and mutated in human cancer, including lung and breast cancer, and plays an important role in the growth of cancer cells and in resistance to chemotherapy.
EGFR becomes activated when the epidermal growth factor (EGF) - its ligand or partner molecule - binds to it and triggers biochemical signals within cells that lead to tumor growth or resistance to treatment. In human cancers, the EGFR may be expressed with or without its ligand or partner.
The researchers found that brain cancer cells expressing EGFR are more resistant to chemotherapy in the absence of ligand. Specifically, the presence of EGF acts as a switch to turn off non-canonical signaling and turn on ligand-activated signaling. Non-canonical EGFR signaling results in activation of a transcription factor called IRF3. IRF3 activity activates immune signals and normally protects cells from virus infection but when activated in cancer cells may protect tumor cells from chemotherapy. Therefore, the IRF3 signaling network may be a new target for treatment in cancer.