Naiara Perurena, PhD, PharmD
Brigham and Women’s Hospital – Harvard Medical School
Around 15-20% of breast cancers are characterized by the amplification or overexpression of the receptor tyrosine kinase HER2 and are therefore classified as HER2-positive. In these tumors, HER2 drives tumor formation and progression by activating an oncogenic signaling cascade. Fortunately, the development of therapeutic agents that directly target HER2 has substantially improved the clinical outcome of individuals with HER2-positive breast cancer. Nevertheless, resistance to HER2 inhibitors remains a major challenge, especially in the metastatic setting.
Currently, there are no cures for metastatic breast cancer. In addition, while many individuals with localized disease initially respond to HER2-directed therapies, a subset of patients with no overt signs of metastasis may still relapse. Therefore, there is an urgent need to 1) understand the mechanisms that underlie resistance to current treatments, 2) identify robust biomarkers of therapeutic resistance, and 3) develop improved, and more importantly, curative therapies.
As a Terri Brodeur Fellow, Dr. Perurena aims to define the role of two new tumor suppressor RasGAPs in anti-HER2 resistance. We have previously shown that the loss of these RasGAPs promotes primary tumor growth and metastasis through the activation of AKT, ERK and NF-kB signaling pathways. Interestingly, all three of these pathways have been implicated in resistance to anti-HER2 therapies. Therefore, we hypothesized that the loss of these RasGAPs might not only drive metastasis but also induce resistance to anti-HER2 therapies in breast cancer. Our preliminary data support this hypothesis. The overall goals of the project are to: 1) determine how the loss of these proteins precisely promotes resistance to anti-HER2 therapies and 2) identify new targets in these RasGAP-deficient tumors so that we may develop more effective combination therapies.
Dr. Perurena obtained her Pharm.D. in 2010 from the University of Navarra (Pamplona, Spain) after completing an internship at St. George’s Hospital (London, UK). She completed her Ph.D. in 2015 under the supervision of Dr. Lecanda at the Center for Applied Medical Research (Pamplona, Spain). During her Ph.D. she studied molecular mechanisms of metastasis and received a fellowship to join Dr. Egeblad’s laboratory at Cold Spring Harbor Laboratory as a visiting student.
Since 2016, Dr. Perurena is a postdoctoral research fellow in the laboratory of Dr. Cichowski at Brigham and Women’s Hospital/Harvard Medical School.