Epiregulin
TGFa
Betacellulin
Epigen
Neuregulin 2
Neuregulin 4
Potential for a targeted EGFR-inhibitor
When it comes to neuropathic pain: Not all EGFR-inhibitors are created equal – a window of opportunity?
EGFR-inhibitors are well tolerated, but for some patients, side effects in the skin or the gastrointestinal system make long-term treatment challenging.
It is therefore of interest that several patients experience improved pain relief, less side effects and need only half of the recommended oncologic dose of certain EGFR-inhibitors.
Mode of action
in neuropathic pain
Since the serendipitous discovery that EGFR-inhibition leads to relief of neuropathic pain, at least five research groups have independently confirmed and/or explained the mode of action.
Although several of the EGFR's activating mechanisms, downstream signaling mediators, and end targets have been implicated, the EGFR itself has consistently been found to be critical in neuropathic pain.
Activation of the EGFR upon nerve damage, leading to translocation of critical ion channels and hyperexcitability of these neurons, is the most likely mechanism.
The EGFR Timeline
from Oncology into Neurology
Discovery of the EGFR. Stanley Cohen awarded the Nobel Prize in Medicine in 1986.
Discovery of the EGFR. Stanley Cohen awarded the Nobel Prize in Medicine in 1986.
Hypothesis: Reduction in neuropathic pain through EGFR-inhibition.
Incidental reduction in peripheral neuropathy reported in EGFR-inhibitor trial results.
Incidental reduction in peripheral neuropathy reported in EGFR-inhibitor trial results.
Incidental reduction in peripheral neuropathy reported in EGFR-inhibitor trial results.
Incidental reduction in peripheral neuropathy reported in EGFR-inhibitor trial results.
Like many breakthroughs in the history of medicine, relief of neuropathic pain after treatment with an EGFR-inhibitor was a serendipitous discovery.
Like many breakthroughs in the history of medicine, relief of neuropathic pain after treatment with an EGFR-inhibitor was a serendipitous discovery.
Like many breakthroughs in the history of medicine, relief of neuropathic pain after treatment with an EGFR-inhibitor was a serendipitous discovery.
Like many breakthroughs in the history of medicine, relief of neuropathic pain after treatment with an EGFR-inhibitor was a serendipitous discovery.
A case series describing 20 patients with neuropathic pain treated with EGFR-inhibitors.
A case series describing 20 patients with neuropathic pain treated with EGFR-inhibitors.
A case series describing 20 patients with neuropathic pain treated with EGFR-inhibitors.
A case series describing 20 patients with neuropathic pain treated with EGFR-inhibitors.
1st preclinical confirmation of pain relief through EGFR-inhibition.
Positive signal from a randomized proof of concept trial using EGFR-inhibition to treat neuropathic pain.
Positive signal from a randomized proof of concept trial using EGFR-inhibition to treat neuropathic pain.
Positive signal from a randomized proof of concept trial using EGFR-inhibition to treat neuropathic pain.
Positive signal from a randomized proof of concept trial using EGFR-inhibition to treat neuropathic pain.
The EGFR's potential role in opioid tolerance is first introduced.
Prospective observational study of EGFR-inhibitors in neuropathic cancer pain.