Publications

Activation of AMP-activated protein kinase by EGF receptor 2 - EGF receptor tyrosine kinase inhibitor protects cardiac cells :: June 2007
Numerous targeted therapies have shown cardio-toxicity in a small, but significant number of patients receiving drug. The AMPK pathway is a master regulator of cellular metabolism and mobilizes ATP stores in the failing/stressed heart. Targeted therapies that result in inhibition of AMPK may potentially be associated with cardio-toxicity while those that result in activation of AMPK may protect the heart from the stress caused by drug treatment.

A model of acquired autoresistance to a potent ErbB2 tyrosine kinase inhibitor and a therapeutic strategy to prevent its onset in breast cancer. :: May 2006
In this study, scientists at TMD and GlaxoSmithKline brought together mechanisms of response and resistance defined at the molecular level in breast cancer cell lines with clinical observations. Early-phase clinical trials indicate that clinical response to TykerbT monotherapy in some patients with HER2-overexpressing breast cancers is generally short-lived. This important publication identifies the involvement of enhanced estrogen receptor (ER) signaling in the development of resistance of a HER2 expressing breast cancer cell line to TykerbT. TMD performed all the IHC experiments in this paper, and some of the western blot and cell viability assays. This paper implicated the ER pathway as a major determinant of TykerbT resistance and points to a combination of ErbB inhibition plus anti-hormone therapy as a treatment strategy for women with HER2(+);ER(+) breast cancer.

Study of the Biologic Effects of Lapatinib, a Reversible Inhibitor of ErbB1 and ErbB2 Tyrosine Kinases, on Tumor Growth and Survival Pathways in Patients With Advanced Malignancies :: April 2005
This was a pilot study to assess the biologic effects of lapatinib on various tumor growth/survival pathways in patients with advanced ErbB1 and/or ErbB2-overexpressing solid malignancies.

Epigen, the Last Ligand of ErbB Receptors, Reveals Intricate Relationships between Affinity and Mitogenicity :: March 2005
Four ErbB receptors and multiple growth factors sharing an epidermal growth factor (EGF) motif underlie transmembrane signaling by the ErbB family in development and cancer..

The efficacy of Herceptin therapies is influenced by the expression of other erbB receptors, their ligands and the activation of downstream signalling proteins :: September 2004
ErbB2 and EGFR are attractive oncology therapeutic targets as their overexpression in tumors predicts a poorer clinical outcome in a variety of epithelial malignancies.

Prognostic Significance of Phosphorylated P38 Mitogen-Activated Protein Kinase and HER-2 Expression in Lymph Node-Positive Breast Carcinoma :: February 2004
Development Award from the National Cancer Institute (K23 CA82119). Overexpression of the erbB/HER family of growth factor receptors has been associated with poor prognosis in patients with breast carcinoma.

Synergistic down-regulation of receptor tyrosine kinases by combinations of mAbs: Implications for cancer immunotherapy :: February 2005
The four receptor t y rosine kinases of the ErbB family and their multiple ligand molecules for m a layered signaling net work...