RTKs in Cancer (Con’t) 03/11/2014
EGF Receptor Inhibition
ERBBtargeted therapeutics in clinical use
Trastuzamab (Herceptin) – approved for the treatment of ERBB2overexpressing breast cancer, ongoing
trials for use in combination with various other drugs
Cetuximab (Erbitux) – Approved for the treatment of CRC, ongoing in combination with various other drugs
for pancreatic cancer, HNSCC and NSCLC
Panitumumab – trials are ongoing for CRC, RCC and NSCLC
Antisense strategies for ligands are not successful (yet) because:
ErbB2 (neu) receptor does not have a known ligand
Too many ligands crossreact with different receptor\
Tyrosine Kinase Inhibitors
ATP competitive inhibitor of EGFR tyrosine kinase activity
Effectively inhibits HER1HER2 heterodimers
Shenoy et. al Overview
Hypoxia is actually a tumor’s friend
Cancer cells have so many genes that they overexpress that gives them the ability to thrive under hypoxic
Betaarr1 is elevated in breast cancer cells vs. Hek cells
Erk levels are going to be very different; why is this their housekeeping protein?
They used an Ab that they generated. Both Abs are not specific for the isoforms.
What did they quantify it to? Input? What does that mean?
Also, you want to use a nonmalignant breast epithelial cell
Tissue microarray Figure 2
Does betaarrestin play a role in metastasis?
Is it a scrambled control? This might be nontransfected which isn’t okay, you have to make sure the
scrambled insertion doesn’t screw anything