Dr. Lauring and colleagues are building upon the pioneering cancer genetics research completed at the Kimmel Cancer Center that revealed the unique genetic blueprint of breast cancer. He is studying recurrent genetic alterations in cancer cells, including mutations and large-scale chromosomal changes. He has identified mutant genes to which certain types of cancer cells become addicted; that is, the tumors growth and survival is directly tied to these mutant genes. In some cases, these mutant genes are abnormally active and can be successfully targeted with therapy. A well-known example of this in breast cancer is the Her-2 gene. Her-2 is over-expressed in about 15 percent of breast cancers and found to play an important role in the progression of the cancer. As a result, a number of active drugs targeting the Her-2 protein have been developed and have dramatically improved survival for this type of breast cancer. Dr. Lauring is hoping to uncover other targets that may have similar potential for extending survival.
Currently, he is studying mutant genes and chromosomes in human breast cancer cells and cell lines to better understand how the alterations foster abnormal cell growth and the aggressiveness of tumors. These cell lines will serve as model systems to study drugs or other interventions for their ability to selectively inhibit the growth of breast cancers containing that specific mutant gene. Dr. Lauring and team are currently studying a number of altered genes related to the most common type of breast cancer, known as ER-positive or hormone receptor positive breast cancer. This important research is helping to determine if these mutant genes contribute to sensitivity or resistance to widely used hormonal therapies, such as tamoxifen.
Konishi, H.; Karakas, B.; Abukhdeir, A.M.; Lauring, J.; Gustin, J.P.; Garay, J.P.; Konishi, Y.; Gallmeier, E.; Bachman, K.E.; Park, B.H. Knock-in of mutant K-ras in nontumorigenic human epithelial cells as a new model for studying K-ras mediated transformation. Cancer Res. 2007 Sep 15;67(18):8460-8467.
Konishi, H.; Lauring, J.; Garay, J.P.; Karakas, B.; Abukhdeir, A.M.; Gustin, J.P.; Konishi, Y.; Park, B.H. A PCR-based high-throughput screen with multiround sample pooling: application to somatic cell gene targeting. Nat Protoc. 2007;2(11):2865-2874.
Abukhdeir, A.M.; Vitolo, M.I.; Argani, P.; De Marzo, A.M.; Karakas, B.; Konishi, H.; Gustin, J.P.; Lauring, J.; Garay, J.P.; Pendleton, C.; Konishi, Y.; Blair, B.G.; Brenner, K.; Garrett-Mayer, E.; Carraway, H.; Bachman, K.E.; Park, B.H. Tamoxifen-stimulated growth of breast cancer due to p21 loss. Proc Natl Acad Sci U S A. 2008 Jan 8;105(1):288-293.
Lauring, J.; Abukhdeir, A.M.; Konishi, H.; Garay, J.P.; Gustin, J.P.; Wang, Q.; Arceci, R.J.; Matsui, W.; Park, B.H. The multiple myeloma associated MMSET gene contributes to cellular adhesion, clonogenic growth, and tumorigenicity. Blood. 2008 Jan 15;111(2):856-864.
Gustin, J.P.; Karakas, B.; Weiss, M.B.; Abukhdeir, A.M.; Lauring, J.; Garay, J.P.; Cosgrove, D.; Tamaki, A.; Konishi, H.; Konishi, Y.; Mohseni, M.; Wang, G.; Rosen, D.M.; Denmeade, S.R.; Higgins, M.J.; Vitolo, M.I.; Bachman, K.E.; Park, B.H. Knockin of mutant PIK3CA activates multiple oncogenic pathways. Proc Natl Acad Sci U S A. 2009 Feb 24;106(8):2835-2840.
Lauring, J.; Cosgrove, D.P.; Fontana, S.; Gustin, J.P.; Konishi, H.; Abukhdeir, A.M.; Garay, J.P.; Mohseni, M.; Wang, G.M.; Higgins, M.J.; Gorkin, D.; Reis, M.; Vogelstein, B.; Polyak, K.; Cowherd, M.; Buckhaults, P.J.; Park, B.H. Knock in of the AKT1 E17K mutation in human breast epithelial cells does not recapitulate oncogenic PIK3CA mutations. Oncogene. 2010 Apr 22;29(16):2337-2345.
Higgins, M.J.; Beaver, J.A.; Wong, H.Y.; Gustin, J.P.;
Lauring, J.D.; Garay, J.P.; Konishi, H.; Mohseni, M.; Wang, G.M.; Cidado, J.; Jelovac, D.; Cosgrove, D.P.; Tamaki, A.; Abukhdeir, A.M.; Park, B.H. PIK3CA mutations and EGFR overexpression predict for lithium sensitivity in human breast epithelial cells. Cancer Biol Ther. 2011 Feb 1;11(3):35-44.