by amplification of the hepatocyte growth factor receptor, which drives ERBB3 dependent activation of PI3K. Side effects Common Rash occurs in the majority of patients. This resembles acne and primarily involves the face and neck. It is self-limited and resolves in the majority of cases, even with continued use. Some clinical studies have indicated a correlation between the severity of the skin reactions and increased survival though this has not been quantitatively assessed. The Journal of Clinical Oncology reported in 2004 that "cutaneous [skin] rash seems to be a surrogate marker of clinical benefit, but this finding should be confirmed in ongoing and future studies." The newsletter Lung Cancer Frontiers reported in its October 2003 issue, "Patients with moderate to severe cutaneous reactions [rashes] have a far better survival, than those with only mild reactions and much better than those with no cutaneous manifestations of drug effects." Diarrhea Loss of appetite Fatigue Partial hair loss (by strands, not typically in clumps) Rare interstitial pneumonitis, which is characterized by cough and increased dyspnea. This may be severe and must be considered among those patients whose breathing acutely worsens. ingrown hairs, such as eyelashes gastrointestinal tract toxicity serious or fatal gastrointestinal tract perforations skin toxicity bullous, blistering, and exfoliative skin conditions (some fatal) Stevens–Johnson syndrome/toxic epidermal necrolysis ocular disorders corneal lesions Pulmonary toxicity interstitial pneumonitis bronchiolitis obliterans with organizing pneumonia (BOOP) pulmonary fibrosis fatal asymmetric interstitial lung disease Interactions Erlotinib is not a substrate for either of hepatic OATPs (OATP1B1 or OATP1B3). Also, erlotinib is not an inhibitor of OATP-1B1 or OATP-1B3 transporter. Erlotinib is mainly metabolized by the liver enzyme CYP3A4. Compounds which induce this enzyme (i.e. stimulate its production), such as St John's wort, can lower erlotinib concentrations, while inhibitors can increase concentrations. Mechanism Erlotinib is an epidermal growth factor receptor inhibitor (EGFR inhibitor). The drug follows Iressa (gefitinib), which was the first drug of this type. Erlotinib specifically targets the epidermal growth factor receptor (EGFR) tyrosine kinase, which is highly expressed and occasionally mutated in various forms of cancer. It binds in a reversible fashion to the adenosine triphosphate (ATP) binding site of the receptor. For the signal to be transmitted, two EGFR molecules need to come together to form a homodimer. These then use the molecule of ATP to trans-phosphorylate each other on tyrosine residues, which generates phosphotyrosine residues, recruiting the phosphotyrosine-binding proteins to EGFR to assemble protein