Small Molecule Kinase Inhibitors Part 2 Flashcards
HER Family of Receptors
HER 1 = EGFR and HER2 have been targeted for therapy
HER3 and HER4 have NOT been targeted yet
When activated, they are able to transduce oncogenic signals and cause proliferation in cancers like lung and breast cancer
Erlotinib Brand and PK
- Tarceva
- SMKI specific for EGFR
- Bioavailability is increased by food to almost 100%
- Metabolized by the liver
- Smokers have a 24% higher rate of clearance
Erlotinib Drug Interactions
• CYP3A4 Inhibitors and inducers are expected to increase drug exposure or clearance
Erlotinib Clinical Indication
Non-Small Cell Lung Cancer (NSCLC)
Metastatic pancreatic cancer in combo with gemcitabine
Erlotinib Severe AE
GI Perforations
Renal disorder
Hepatic disorder
Ocular disorders (corneal ulcerative and abnormal eyelash growth)
Lapatinib Brand and Target
TYKERB
SMKI specific for HER2/EGFR
Lapatinib Indication
Advanced or metastatic breast cancer with capecitabine
Lapatinib AE
Cardiac toxicity
Hepatoxicity
Interstitial lung disease/pneumonitis
Laptainib Drug Interactions
- It inhibits CYP3A4 and CYP 2C8 and Pgp
* Inducers of CYP3A4 and Pgp
VEGF Family and Receptors
VGFR 1, 2, and 4 are most important because when these are activated, then you will see new blood vessel generation (aka, this provides blood supply and nutrition to cancer)
So inhibiting these does not directly kill the cancer but you are cutting off the blood vessel formation
Sunitinib Brand and Target
Sutent
SMKI for multi-tyrosine kinases
Sunitinib Clinical Indication
GIST
Metastatic Renal Cell Carcinoma (MRCC)
Sunitinib AE
BROAD: fever, mucositis, elevated LFTs
Sunitinib Drug Interactions
CYP3A4 inhibitors and inducers
Sorafenib Brand and Target
Nexavar
SMKI for mutliple tyrosine/serine/threonine kinases
