Kathryn B. Horwitz, PhD

2008-2009 BCRF Project:
(made possible by generous support from Play For P.I.N.K.)

At present, the role of hormones in metastasis is unknown because there are no good models for study. With BCRF support, Dr. Horwitz and her team are developing models of ER+, PR+ breast cancer metastasis that more accurately reflect the clinical situation. They have defined putative breast cancer stem cells in ER+, PR+ breast cancers. Importantly, the stem cells lack hormone receptors. This suggests that cancer stem cells in hormone dependent breast cancers would survive hormone therapies, allowing them to repopulate a tumor. Progestins commonly used for menopausal hormone replacement therapies (HRT), increase cancer stem cells, perhaps explaining why some HRTs increase breast cancer risk. The researchers will now further characterize breast cancer stem cells as a prelude to finding ways to kill them.

For the coming year, Dr. Horwitz will focus on breast cancer metastasis, and breast cancer stem cells. Her team’s first aim is to develop models of ER+ metastasis, so that they can study the effect of hormones and hormonal treatments on the metastatic process itself, and on growth of cancer cells at distant sites. In the second part of their project, they focus on cancer stem cells, a sub-population of cells (1% or less) within a tumor that slowly renew themselves, and can also throw off more rapidly dividing progeny that fuel the tumor’s growth. It is believed that cancer stem cells are capable of unlimited growth and drive disease recurrence and metastasis. Dr. Horwitz and colleagues find that even in ER+ breast cancers, the stem cells are ER−. This means that you can kill off 99% of an ER+ cancer with hormone therapies, but the stem cells would survive to repopulate the tumor, or to spread cancer to metatastic sites.

Over the coming year they aim to characterize breast cancer stem cells in more detail using permanent cell lines and patient samples. As part of this aim, they will demonstrate whether the cells expanded by progestins exhibit the properties of cancer stem cells.

Bio:
Dr. Horwitz is a graduate of Barnard College, received a Master's degree from New York University, and a Doctoral degree from the University of Texas, Southwestern Medical School in Dallas. She then joined the Department of Medicine faculty at the University of Colorado's School of Medicine, where she was rapidly promoted to Professor. She has received many awards and recognitions for her work. The University of Colorado has recognized her extensive service to the University, and to the local, national and international community of scientists and patients, by naming her a 'Distinguished Professor' of the University, an accolade reserved for only a handful of professors on the four University campuses.