Schweppe, RE, Klopper, JP, Korch, C, Pugazhenthi, U,
Benezra, M, Knauf, JA, Fagin, JA, Marlow, L, Copland, JA, Smallridge, RC, and
BR Haugen. DNA Profiling Analysis of 40 Human Thyroid Cancer Cell Lines
Reveals Cross-Contamination Resulting in Cell Line Redundancy and
Misidentification. 2008. J. Clin. Endocrinol. Metab., 93: 4331-4441. [PMID:
Schweppe, RE, Kerege, A, Sharma, V, Poczobutt, JM,
Gutierrez-Hartmann, A, Grzywa, RL, and BR Haugen. Distinct Genetic
Alterations in the MAPK Pathway Dictate Sensitivity of Thyroid Cancer Cells to
MKK1/2 Inhibition. 2009. Thyroid., 19: 825-83 [PMID: 19500021].
Schweppe, RE, French, JD, Kerege, AA, Sharma, V, Grzywa, RL,
and BR Haugen. Inhibition of Src with AZD0530 Reveals the Src-Focal
Adhesion Kinase as a Therapeutic Target in Papillary and Anaplastic Thyroid
Carcinoma. 2009. J. Clin. Endocrinol. Metab., 94: 2199-2203 [PMID: 19293266].
Schweppe, RE. Thyroid Cancer Cell Lines:
Critical Models to Study Thyroid Cancer Biology and New Therapeutic Targets.
2012. Frontiers in Cancer Endocrinology, 3:81. [PMID: 22723793].
Chan, CM, Jing, X, Pike, LA, Zhou,Q, Lim, D-J,
Sams, SB, Lund,GA, Sharma, V, Haugen, BR, and RE Schweppe. Targeted
Inhibition of Src Kinase with Dasatinib Blocks Thyroid Cancer Growth and
Metastasis. 2012. Clin Cancer Res., 18:3580-3591 [PMID: 22586301]
The focus of my lab is to identify novel molecular targets relevant to papillary and anaplastic thyroid cancer (PTC and ATC) with the ultimate goal of advancing these studies to clinical trials for thyroid cancer patients who do not respond to standard treatments. Much attention has been devoted to the mitogen activated protein kinase (MAPK) pathway as a therapeutic target due to the large percentage of activating mutations in this pathway (BRAF, RAS, RET/PTC), yet the efficacy of MAP kinase pathway inhibitors in thyroid cancer has thus far been limited. The Focal Adhesion Kinase (FAK)-Src pathway has emerged as a major player in cancer progression, especially relating to metastasis, yet how FAK and Src promote disease progression and the metastatic process is not well understood. Our lab recently discovered that FAK is overexpressed and phosphorylated in thyroid tumor samples, which provided the necessary justification to pursue this pathway as an alternative, clinically relevant target in thyroid cancer (Schweppe et al 2009). We have further shown that the majority of cell lines derived from advanced thyroid cancer patients exhibit high levels of phospho-FAK and that inhibition of the FAK-Src pathway blocks growth and invasion in cells with high phospho-FAK. Importantly, we found that FAK/Src signals independently of the MAP kinase pathway, suggesting that the FAK-Src pathway may represent a second independent risk factor for thyroid cancer patients, especially in relation to tumor aggressiveness and metastatic spread.
TJ Beadnell (Cancer Biology graduate student)
Brittelle Kessler (Cancer Biology graduate student)
McKenna (Surgery Resident)
Mishall (Cancer Biology Student)
Laura Pike (Senior Professional Research Assistant)
Vibha Sharma (Research Associate)
Kelsey Wuensch (Professional Research Assistant)