CRAF inhibition induces apoptosis in melanoma cells with non-V600E BRAF mutationsK S M Smalley
The Wistar Institute, Philadelphia, PA, USA
Oncogene 28:85-94. 2009
..In summary, we have identified a group of melanomas with low-activity BRAF mutations that are reliant upon CRAF-mediated survival activity...
- Increased cyclin D1 expression can mediate BRAF inhibitor resistance in BRAF V600E-mutated melanomas
Keiran S M Smalley
The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA
Mol Cancer Ther 7:2876-83. 2008
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- Identification of a novel subgroup of melanomas with KIT/cyclin-dependent kinase-4 overexpression
Keiran S M Smalley
The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA
Cancer Res 68:5743-52. 2008
..This group of melanomas may be a subpopulation for which imatinib or other KIT inhibitors may constitute optimal therapy...
- Ki67 expression levels are a better marker of reduced melanoma growth following MEK inhibitor treatment than phospho-ERK levels
K S M Smalley
The Wistar Institute, 3601 Spruce Street, Philadelphia, Pennsylvania, 19104, USA
Br J Cancer 96:445-9. 2007
..Here, we demonstrate that there is a poor correlation between pERK inhibition and the anti-proliferative effects of MEK inhibitors in melanoma cells. We suggest that Ki67 is a better biomarker for future clinical studies...
- Notch1 signaling promotes primary melanoma progression by activating mitogen-activated protein kinase/phosphatidylinositol 3-kinase-Akt pathways and up-regulating N-cadherin expression
Zhao-Jun Liu
The Wistar Institute, Philadelphia, Pennsylvania 19104, USA
Cancer Res 66:4182-90. 2006
..Our data show regulation of MAPK/PI3K-Akt pathway activities and expression of N-cadherin by the Notch pathway and provide a mechanistic basis for Notch signaling in the promotion of primary melanoma progression...
- Multiple signaling pathways must be targeted to overcome drug resistance in cell lines derived from melanoma metastases
Keiran S M Smalley
The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA
Mol Cancer Ther 5:1136-44. 2006
..It is further suggested that BRAF mutational status is not predictive of response to MEK inhibition under three-dimensional culture conditions...
- The mitogen-activated protein/extracellular signal-regulated kinase kinase inhibitor AZD6244 (ARRY-142886) induces growth arrest in melanoma cells and tumor regression when combined with docetaxel
Nikolas K Haass
The Wistar Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
Clin Cancer Res 14:230-9. 2008
..This study addresses the anti-melanoma activity of the MEK inhibitor AZD6244 (ARRY-142886)...
- Towards the targeted therapy of melanoma
K S M Smalley
The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA
Mini Rev Med Chem 6:387-93. 2006
..The recent years have seen great advances in understanding the biology of melanoma. In the current review we discuss the most promising molecular targets for melanoma and suggest possible strategies for overcoming resistance...
- Life isn't flat: taking cancer biology to the next dimension
Keiran S M Smalley
The Wistar Institute, Philadelphia, Pennsylvania 19104, USA
In Vitro Cell Dev Biol Anim 42:242-7. 2006
..It is likely that the adoption of these and other 3D models will allow us to more closely re-create the behavior of the tumor in vivo which may lead to identifying better anticancer drug candidates at an earlier stage of development...
- The essential role of fibroblasts in esophageal squamous cell carcinoma-induced angiogenesis
Kazuhiro Noma
The Wistar Institute, Philadelphia, Pennsylvania 19104, USA
Gastroenterology 134:1981-93. 2008
..Esophageal squamous cell carcinoma (ESCC) is known to be a highly angiogenic tumor. Here, we investigated the role of the stromal fibroblasts in the ESCC-induced angiogenic response using a novel 3-dimensional model...
- Dysregulation of claudin-7 leads to loss of E-cadherin expression and the increased invasion of esophageal squamous cell carcinoma cells
Mercedes Lioni
The Wistar Institute, 3601 Spruce St, Philadelphia, PA 19104, USA
Am J Pathol 170:709-21. 2007
..We also demonstrate a critical role for claudin-7 expression in the regulation of E-cadherin in these cells, suggesting this may be one mechanism for the loss of epithelial architecture and invasion observed in esophageal SCC...
- Targeting intracellular signaling pathways as a novel strategy in melanoma therapeutics
Keiran S M Smalley
The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA
Ann N Y Acad Sci 1059:16-25. 2005
..In the current review, we discuss the role for these signaling pathways in melanoma and discuss the rationale for targeting signaling cascades using small molecule inhibitors...
- Targeting the stromal fibroblasts: a novel approach to melanoma therapy
Keiran S M Smalley
The Wistar Institute, Philadelphia, PA 19104, USA
Expert Rev Anticancer Ther 5:1069-78. 2005
..More recent thinking posits that, although cancers are initiated through genetic mutation, progression is often the result of dynamic interactions between the tumor cells and their surrounding environment...
- Up-regulated expression of zonula occludens protein-1 in human melanoma associates with N-cadherin and contributes to invasion and adhesion
Keiran S M Smalley
Wistar Institute, 3601 Spruce St, Philadelphia, Pennsylvania 19104, USA
Am J Pathol 166:1541-54. 2005
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- Loitering with intent: new evidence for the role of BRAF mutations in the proliferation of melanocytic lesions
Keiran S M Smalley
The Wistar Institute, Philadelphia, Pennsylvania, USA
J Invest Dermatol 123:xvi-xvii. 2004
- Structure-based design of an organoruthenium phosphatidyl-inositol-3-kinase inhibitor reveals a switch governing lipid kinase potency and selectivity
Peng Xie
Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania, USA
ACS Chem Biol 3:305-16. 2008
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- The great escape: another way for melanoma to leave physiological control?
Keiran S M Smalley
The Wistar Institute, Philadelphia, Pennsylvania, USA
J Invest Dermatol 121:xi-xii. 2003
- The role of altered cell-cell communication in melanoma progression
Nikolas K Haass
The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA
J Mol Histol 35:309-18. 2004
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- Is ERK activation a good biomarker for estradiol and tamoxifen effects?
Keiran S M Smalley
Wistar Institute, Philadelphia, Pennsylvania, USA
Cancer Biol Ther 6:119-20. 2007
- An organometallic protein kinase inhibitor pharmacologically activates p53 and induces apoptosis in human melanoma cells
Keiran S M Smalley
The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA
Cancer Res 67:209-17. 2007
..Taken together, our data provide a new strategy for the pharmacologic activation of p53 in melanoma, which may be a viable approach for overcoming apoptotic resistance in melanoma and offer new hope for rational melanoma therapy...
- Adhesion, migration and communication in melanocytes and melanoma
Nikolas K Haass
The Wistar Institute, Philadelphia, PA 19104, USA
Pigment Cell Res 18:150-9. 2005
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- Bortezomib induces apoptosis in esophageal squamous cell carcinoma cells through activation of the p38 mitogen-activated protein kinase pathway
Mercedes Lioni
The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA
Mol Cancer Ther 7:2866-75. 2008
..We therefore suggest that p38 MAPK pathway activation is an excellent potential therapeutic strategy in ESCC. It is further suggested that bortezomib could be added to existing ESCC therapeutic regimens...
- Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity
James Tsai
Plexxikon, Inc, 91 Bolivar Drive, Berkeley, CA 94710, USA
Proc Natl Acad Sci U S A 105:3041-6. 2008
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- Demonstration of a genetic therapeutic index for tumors expressing oncogenic BRAF by the kinase inhibitor SB-590885
Alastair J King
Department of Oncology, MMPD CEDD, GlaxoSmithKline, Collegeville, Pennsylvania 19426, USA
Cancer Res 66:11100-5. 2006
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- A pivotal role for ERK in the oncogenic behaviour of malignant melanoma?
Keiran S M Smalley
Section of Medicine, Institute of Cancer Research, London, United Kingdom
Int J Cancer 104:527-32. 2003
..The aim of the current review is to assess the role of ERK in melanoma behaviour and to determine whether modulation of these kinases could offer new therapeutic opportunities...
- Farnesyl transferase inhibitor SCH66336 is cytostatic, pro-apoptotic and enhances chemosensitivity to cisplatin in melanoma cells
Keiran S M Smalley
Section of Medicine, Institute of Cancer Research, London, England
Int J Cancer 105:165-75. 2003
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- Rewired ERK-JNK signaling pathways in melanoma
Pablo Lopez-Bergami
Signal Transduction Program, The Burnham Institute for Medical Research, La Jolla, CA 92037, USA
Cancer Cell 11:447-60. 2007
..Our data reveal that, in human melanoma, the rewired ERK signaling pathway upregulates JNK and activates the c-Jun oncogene and its downstream targets, including RACK1 and cyclin D1...
- Farnesyl thiosalicylic acid inhibits the growth of melanoma cells through a combination of cytostatic and pro-apoptotic effects
Keiran S M Smalley
Section of Medicine, Institute of Cancer Research, London, England
Int J Cancer 98:514-22. 2002
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