Any research in RPGN and glomerular diseases that can possibly
lead to any new drug development are good to review. A recent study in Nature
Medicine diseases the role of the heparin binding epidermal growth factor like
growth factor in the role of glomerular disease. The researchers in this paper
showed denovo induction of heparin-binding epidermal growth factor–like
growth factor (HB-EGF) in intrinsic glomerular epithelial cells (podocytes) from
both mice and humans with RPGN. HB-EGF induction increases phosphorylation of
the epidermal growth factor receptor (EGFR) in mice with RPGN. In mice without
the activation of HB-EGF and no EGFR receptor activation, course of RPGN is
improved. Conditional deletion of the Egfr gene from
podocytes of mice alleviated the severity of RPGN. Pharmacologic blockaded of
the EGFR also can alleviate RPGN.
When these receptors are taken out of the equation- the disease
doesn't take full form.
There are EGFR receptor antagonist that are being used. Not for RPGN
but for cancers.
The epidermal growth factor receptor is a
member of the ErbB family of receptors, a subfamily of four closely
related the tyrosine kinases. Upregulation has led to colon, breast and
neurological cancers.
There are many anticancer therapeutics directed
against EGFR, including gefitinib and erlotinib for lung
cancer, and cetuximab for colon cancer. Cetuximab is a monoclonal antibody inhibitor. This allows for tyrosine kinase inhibition as well leading to treating the cancer.
As we think these above agents might be
beneficial for RPGN, we have to be careful as the first method is a tyrosine
kinase inhibitor approach which can have renal side effects as pre eclampsia
like syndromes, hypertension and thrombotic microangiopathies.
This is where Oncology and Nephrology are at the
forefront of sharing information. Congrats on a nicely designed study.
Ref:
http://www.nature.com/nm/journal/vaop/ncurrent/full/nm.2491.html
Image source: http://www.mc.vanderbilt.edu/lens/article/?id=204
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