Lapatanib -: Oncolytic -: Dual EGFR and erbB-2 inhibitor

Human epidermal growth factor receptor (EGFR) and erbB-2 are subclass I receptor tyrosine kinases that have been linked with a number of cancers, thereby making inhibitors of these proteins attractive targets for drug development. Several signaling cascades are associated with EGFR, which plays a role in mitogenesis, apoptosis, cell migration, differentiation and angiogenesis, all important processes in tumorigenesis. EGFR and its ligands are overexpressed in a number of solid tumors, including pancreatic, lung, ovarian, renal, gastric, hepatic and breast cancer. ErbB-2 overexpression has been found in a wide variety of cancers, including breast, bladder, colorectal, gastric, ovarian, prostate, renal and uterine cancers. Agents that target EGFR and erbB-2 are therefore under development or currently available for a number of cancer indications. One such agent is lapatinib, a potent and reversible dual EGFR and erbB-2 inhibitor that has shown promising pharmacological activity and pharmacokinetics. Lapatinib has been investigated as an anticancer monotherapy, as well as in combination with trastuzumab, capecitabine, letrozole, paclitaxel and FOLFIRI (irinotecan, 5-fluorouracil and leucovorin), in a number of clinical trials. It is currently in phase III testing for the oral treatment of metastatic breast, head and neck, lung, gastric, renal and bladder cancer. Additional trials of lapatinib in patients with brain, gallbladder, prostate, ovarian, endometrial and hepatobiliary cancers are also under way.