Laura A. Stabile, PhD

Research Associate Professor

2.32b Hillman Cancer Center
5117 Centre Avenue, PA 15232
Phone: 412-623-2015
Fax: 412-623-7768

Education

BA (Chemistry, Spanish), Washington & Jefferson College, Washington, PA, 1993
MS (Biochemistry), West Virginia University, Morgantown, WV, 1995
PhD (Biochemistry), West Virginia University, Morgantown, WV, 1999

Links

Laura A. Stabile, PhD

The translational research activities of the Stabile Laboratory focus on the role of growth factors and hormones in the development of upper aerodigestive tract malignancies (head and neck cancer and lung cancer), with the overall goal of identifying effective targeted therapies for cancer treatment and prevention.

Lung cancer is the leading cause of cancer-related deaths in both men and women worldwide, with a 5-year survival of only 18%. For women, lung cancer has a higher annual mortality rate than breast, uterine and ovarian cancers combined. Sex differences in lung cancer incidence, presentation and survival suggest that sex hormones such as estrogen are critical in the formation of tumors in women’s lungs. Our preclinical findings have identified that estrogen receptors and aromatase (the enzyme that catalyzes the final step in estrogen synthesis) are expressed in lung cancer cells and that estrogen signaling is important in inducing growth in lung tumor mouse models as well as contributing to the spread of the disease in lung cancer patients. We and others have shown that the antiestrogen fulvestrant and aromatase inhibitors can inhibit lung tumor growth and prevent lung tumorigenesis in murine models. We have further demonstrated both genomic and non-genomic effects of estrogen in the lung cancer cells and have elucidated cross-talk between the estrogen signaling pathway and multiple growth factor pathways including epidermal growth factor receptor, fibroblast growth factor receptor, hepatocyte growth factor and vascular endothelial growth factor. These preclinical studies have led to clinical trials examining the effectiveness of the anti-estrogen fulvestrant combined with targeted therapies for advanced stage lung cancer.

Dr. Stabile’s laboratory is currently focused on how estrogen interacts with the immune system in the tumor microenvironment to play a role in the development of lung cancer. Recent studies suggest that estrogen activity on non-tumor cells within the lung tumor microenvironment plays an important role in tumor progression by promoting a protumor immunosuppressive phenotype that allows the tumor to evade the immune system. Immune-based therapies that block checkpoint signals such as programmed death 1 (PD-1) and programmed death-ligand 1 (PD-L1) have revolutionized treatment for lung cancer. PD-L1 binding to PD-1 on cytotoxic T cells prevents the activation of cytotoxic T cells, allowing tumors to escape the adaptive immune response. Checkpoint blockade can offer durable remissions, but only 20% of patients with advanced lung cancer respond to single checkpoint inhibitor-based immunotherapy, and resistance is often observed. The efficacy of current immunotherapeutic agents in lung cancer patients may be enhanced with anti-estrogen agents that are traditionally used for breast cancer treatment.

Current research interests include:

1) Elucidating the mechanistic link between pulmonary inflammation and estrogen signaling in lung carcinogenesis

2) Identification of dietary and other lifestyle factors that modify lung cancer risk, particularly in non-smoking women

3) Development of novel lung cancer therapeutic and prevention strategies involving hormonal manipulation combined with anti-inflammatory agents or immunotherapy

4) Understanding the mechanisms that lead to lung cancer brain metastases, particularly the role of the hepatocyte growth factor/cMET pathway 

  
Sex Differences in the Epidemiology and Biology of Lung Cancer Presentation. Compared to men, women are more likely than men to be diagnosed at a younger age, more likely to be never smokers and to have adenocarcinoma histology compared with other histological subtypes. In addition, among patients with lung adenocarcinoma that have the multitude of driver mutations, women are more likely than men to have tumors with EGFR and KRAS driver mutations. Many hypotheses have been studied to understand the biology behind these differential effects. Some of them include differences in tobacco carcinogen metabolism and DNA repair capacity between men and women.  We are interested in the hormonal effects that may contribute to lung cancer, specifically estrogen signaling. 

Stabile LP, Farooqui M, Kanterewicz B, Abberbock S, Kurland BF, Diergaarde B and Siegfried JM. Preclinical evidence for combined use of aromatase inhibitors and NSAIDs as preventive agents of tobacco-induced lung cancer. J Thorac Oncol 13:399-412, 2018.
Rothenberger NJ, Somasundaram A and Stabile LP.  The role of the estrogen pathway in the tumor microenvironment. Int J Mol Sci 19, 2018.
Siegfried JM, Farooqui M, Rothenberger NJ, Dacic S and Stabile LP. Interaction between the estrogen receptor and fibroblast growth factor receptor pathways in non-small cell lung cancer. Oncotarget 8:24063-24076, 2017.
Stabile LP, Egloff AM, Gibson MK, Gooding WE, Ohr J, Zhou P, Rothenberger NJ, Wang L, Geiger JL, Flaherty JT, Grandis JR and Bauman JE. IL6 is associated with response to dasatinib and cetuximab: Phase II clinical trial with mechanistic correlatives in cetuximab-resistant head and neck cancer. Oral Oncol 69:38-45, 2017.
Siegfried JM, Lin Y, Diergaarde B, Lin HM, Dacic S, Pennathur A, Weissfeld JL, Romkes M, Nukui T and Stabile LP. Expression of PAM50 genes in lung cancer: evidence of interactions between hormone receptors and HER2/HER3 contribute to poor outcome. Neoplasia 17:817-825, 2015.
Stabile LP, Rothstein ME, Cunningham DE, Land SR, Dacic S, Keohavong P and Siegfried JM. Prevention of tobacco carcinogen-induced lung cancer in female mice using antiestrogens.  Carcinogenesis 33:2181-2189, 2012.
Stabile LP, S Dacic, SR Land, DE Lenzner, R Dhir, M Acquafondata, RJ Landreneau, JR Grandis and JM Siegfried.  Combined analysis of estrogen receptor ß-1 and progesterone receptor expression identifies lung cancer patients with poor outcome.  Clin Cancer Res 17:154-164, 2011.
Stabile JP, ME Rothstein, P Keohavong, D Lenzner, SR Land, AL Gaither-Davis, KJ Kim, N Kaminiski and JM Siegfried.  Targeting of both the c-Met and EGFR pathways results in additive inhibition of lung tumorigenesis in transgenic mice.  Cancers (Basel) 2:2153-2170, 2010.