The EGFR and its
HER receptor family members

The EGFR is one of the most studied molecules in the human body.

It receives information from extracellular ligands and/or ligand independent activation, such as via SRC kinases, and transmits these signals into the cell, thereby modulating the cell’s behavior.

The EGFR can signal with another EGFR (its “twin”), as a homodimer, or it can signal with one of the other 3 HER family receptors, as a heterodimer.

EGF
Epiregulin
TGFa
Amphiregulin
Betacellulin
HB-EGF
Epigen
Neuregulin 1
Neuregulin 2
Neuregulin 3
Neuregulin 4
Swipe to see the full figure
The EGFR and its HER receptor family members

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 can be too toxic for long term use in non-cancer patients. AKIGAI founders have generated preclinical and clinical observations supporting the development of modified EGFR inhibitors that are targeted for the treatment of neuropathic pain. These modifications can lead to better pain relief, less side effects and better market protection.

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.

Read study
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.

Read study
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.

Read the full story of the first patient
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.

Read study
Read study
1st EGFR-inhibitor approved for use in oncology.

1st EGFR-inhibitor approved for use in oncology.

Read study
1st EGFR-inhibitor approved for use in oncology.

1st EGFR-inhibitor approved for use in oncology.

Read study
1st EGFR-inhibitor approved for use in oncology.

1st EGFR-inhibitor approved for use in oncology.

Read the full story of the first patient
1st EGFR-inhibitor approved for use in oncology.

1st EGFR-inhibitor approved for use in oncology.

Read study
Read study
Hypothesis: Reduction in neuropathic pain through EGFR-inhibition.

Hypothesis: Reduction in neuropathic pain through EGFR-inhibition.

Read study
Hypothesis: Reduction in neuropathic pain through EGFR-inhibition.

Hypothesis: Reduction in neuropathic pain through EGFR-inhibition.

Read study
Hypothesis: Reduction in neuropathic pain through EGFR-inhibition.

Hypothesis: Reduction in neuropathic pain through EGFR-inhibition.

Read the full story of the first patient
Hypothesis: Reduction in neuropathic pain through EGFR-inhibition.

Hypothesis: Reduction in neuropathic pain through EGFR-inhibition.

Read study
Read study
Incidental reduction in peripheral neuropathy reported in EGFR-inhibitor trial results.

Incidental reduction in peripheral neuropathy reported in EGFR-inhibitor trial results.

Read study
Incidental reduction in peripheral neuropathy reported in EGFR-inhibitor trial results.

Incidental reduction in peripheral neuropathy reported in EGFR-inhibitor trial results.

Read study
Incidental reduction in peripheral neuropathy reported in EGFR-inhibitor trial results.

Incidental reduction in peripheral neuropathy reported in EGFR-inhibitor trial results.

Read the full story of the first patient
Incidental reduction in peripheral neuropathy reported in EGFR-inhibitor trial results.

Incidental reduction in peripheral neuropathy reported in EGFR-inhibitor trial results.

Read study
Read study
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.

Read study
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.

Read study
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.

Read the full story of the first patient
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.

Read study
Read study
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.

Read study
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.

Read study
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.

Read the full story of the first patient
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.

Read study
Read study
1st preclinical confirmation of pain relief through EGFR-inhibition.

1st preclinical confirmation of pain relief through EGFR-inhibition.

Read study
1st preclinical confirmation of pain relief through EGFR-inhibition.

1st preclinical confirmation of pain relief through EGFR-inhibition.

Read study
1st preclinical confirmation of pain relief through EGFR-inhibition.

1st preclinical confirmation of pain relief through EGFR-inhibition.

Read the full story of the first patient
1st preclinical confirmation of pain relief through EGFR-inhibition.

1st preclinical confirmation of pain relief through EGFR-inhibition.

Read study
Read study
PI3K signaling determined to be critical in pain.

PI3K signaling determined to be critical in pain.

Read study
PI3K signaling determined to be critical in pain.

PI3K signaling determined to be critical in pain.

Read study
PI3K signaling determined to be critical in pain.

PI3K signaling determined to be critical in pain.

Read the full story of the first patient
PI3K signaling determined to be critical in pain.

PI3K signaling determined to be critical in pain.

Read study
Read study
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.

Read study
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.

Read study
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.

Read the full story of the first patient
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.

Read study
Read study
The EGFR's potential role in opioid tolerance is first introduced.

The EGFR's potential role in opioid tolerance is first introduced.

Read study
The EGFR's potential role in opioid tolerance is first introduced.

The EGFR's potential role in opioid tolerance is first introduced.

Read study
The EGFR's potential role in opioid tolerance is first introduced.

The EGFR's potential role in opioid tolerance is first introduced.

Read the full story of the first patient
The EGFR's potential role in opioid tolerance is first introduced.

The EGFR's potential role in opioid tolerance is first introduced.

Read study
Read study
Prospective observational study of EGFR-inhibitors in neuropathic cancer pain.

Prospective observational study of EGFR-inhibitors in neuropathic cancer pain.

Read study
Prospective observational study of EGFR-inhibitors in neuropathic cancer pain.

Prospective observational study of EGFR-inhibitors in neuropathic cancer pain.

Read study
Prospective observational study of EGFR-inhibitors in neuropathic cancer pain.

Prospective observational study of EGFR-inhibitors in neuropathic cancer pain.

Read the full story of the first patient
Prospective observational study of EGFR-inhibitors in neuropathic cancer pain.

Prospective observational study of EGFR-inhibitors in neuropathic cancer pain.

Read study
Read study