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Lecture 8

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Department
Pharmacology
Course
Pharmacology 4360A/B
Professor
Moshmi Bhattacharya
Semester
Winter

Description
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  Gefitinib 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  conditions Figure 1 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
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