Grant: Project Grant

Treatment of breast cancer has undergone a revolution with the introduction of therapeutics that specifically targets the initiating oncogene. These include humanized antibodies that bind ErbB2 (Trastuzumab also know as Herceptin) and chemical based inhibitors (Lapatinib) that target ErbB2 function. Amplification and elevated expression of ErbB2 has been implicated as a critical event in breast cancer progression. Recent data also have indicated that somatic mutations with the extracellular domain of ErbB2 that lead to activation of ErbB2 have been noted in a small percentage of human non small cell lung carcinoma. Remarkably, we have previously detected comparable class of activating mutations in ErbB2 in a large proportion mammary tumor arising in transgenic mice expressing an MMTV/ErbB2 transgene. Although comparable activating mutations have not been detected in human breast cancer, we have identified an alternative spliced ErbB2 transcript lacking exon 16 (herein referred to as ErbB2 delta 16) that is expressed in many ErbB2 amplified breast cancer and lung cancer.