Lynne Regan Ph.D.

Recipient of the LUNGevity Foundation/Joan’s Legacy Research Grant. Funded equally by Joan's Legacy and the LUNGevity Foundation.

Lay Description

All cancers result from the aberrant growth of previously normal cells. As the understanding of the molecular basis of cancer develops, scientists are able to identify the specific proteins whose mutation is responsible for the cancerous phenotype. Often, the cause of the cancer is the over-production of proteins that stimulate the cancer cells to grow in an uncontrolled fashion. Two such proteins have been recognized as potentially playing a key role in bronchioalveolar carcinoma (BAC) - HER2 and EGFR. We propose to develop novel methods by which to prevent these proteins being made in the cell, by interfering with the pathway by which they fold. As a result of these studies, we will not only gain a deeper understanding of the molecular basis of BAC, but also make progress towards developing novel therapeutic treatments for the disease.

Scientific Abstract

Bronchioalveolar cancer (BAC) cannot be combated effectively either by surgery or by existing chemotherapies and patients typically die within 5 years of the diagnosis. This proposal seeks to investigate novel, mechanism-based strategies by which to inhibit BAC growth. Although the complete molecular mechanism by which a normal bronchioalveolar cell becomes cancerous is not yet understood, some key elements have been identified. Studies point to the mutation or over-production of the cell-surface proteins, EGFR and HER2 as causative events. There is, however, some discussion as to which of these proteins most correlates with severity of cancer, or even if the two together define the unique features of BAC. We propose to develop a strategy by which to inhibit the correct cellular folding and maturation of both EGFR and HER2. Our approach is to develop novel, small molecule inhibitors of the protein chaperone Hsp90, whose activity is essential for the folding and maturation of both EGFR and HER2. We also propose to compare the effects of our inhibitors alone, and in combination with a different Hsp90 inhibitor (17-AAG), EFGR kinase inhibitors (gefitinib) and HER2 inhibitors (Herceptin). The research we propose has great potential, not only to further elucidate the molecular basis of BAC but also for the development of a new class of anti-cancer agents for use in the treatment of BAC.