H. Lee Moffitt Cancer Center & Research Institute

Faculty Rank:

Assistant Member

USF Affiliations/College Department:

• Medicine / Oncologic Sciences

Research Interests:

The aim of my research is to develop new therapies for the treatment of melanoma. We are integrating genetic and cell signaling information to identify novel subgroups of melanoma and developing novel therapeutic strategies for each of these groups. This work has a translational focus and is very much geared towards getting new compounds into clinical practice.

Publications:

1. Smalley KS. Understanding melanoma signaling networks as the basis for molecular targeted therapy. J Invest Dermatol. 2010 Jan;130(1):28-37. Pubmedid: 19571822.   Pubmed ID: 19571822

2. Flaherty KT, Smalley KS. Preclinical and clinical development of targeted therapy in melanoma: attention to schedule. Pigment Cell Melanoma Res. 2009 Oct;22(5):529-531. Pubmedid: 19619259.   Pubmed ID: 19619259

3. Haass NK, Smalley KS. Melanoma biomarkers: current status and utility in diagnosis, prognosis, and response to therapy. Mol Diagn Ther. 2009;13(5):283-296. Pubmedid: 19791833.   Pubmed ID: 19791833

4. Smalley K, Xiao M, Villanueva J, Nguyen T, Flaherty K, Letrero R, Van BelleP, Elder D, Wang Y, Nathanson K, Herlyn M. CRAF inhibition induces apoptosis in melanoma cells with non-V600E BRAF mutations. Oncogene. 2009 Jan;28(1):85-94. Pubmedid: 18794803.   Pubmed ID: 18794803

5. Smalley KS, Flaherty KT. Development of a novel chemical class of BRAF inhibitors offers new hope for melanoma treatment. Future Oncol. 2009 Aug;5(6):775-778. Pubmedid: 19663727.   Pubmed ID: 19663727

6. Smalley KS, Flaherty KT. Integrating BRAF/MEK inhibitors into combination therapy for melanoma. Br J Cancer. 2009 Feb;100(3):431-435. Pubmedid: 19156138.   Pubmed ID: 19156138

7. Smalley KS, Herlyn M. Integrating tumor-initiating cells into the paradigm for melanoma targeted therapy. Int J Cancer. 2009 Mar;124(6):1245-1250. Pubmedid: 19089923.   Pubmed ID: 19089923

8. Smalley KS, Nathanson KL, Flaherty KT. Genetic subgrouping of melanoma reveals new opportunities for targeted therapy. Cancer Res. 2009 Apr;69(8):3241-3244. Pubmedid: 19351826.   Pubmed ID: 19351826

9. Smalley KS, Sondak VK, Weber JS. c-KIT signaling as the driving oncogenic event in sub-groups of melanomas. Histol Histopathol. 2009 May;24(5):643-650. Pubmedid: 19283671.   Pubmed ID: 19283671

10. Sondak VK, Smalley K. Targeting mutant BRAF and KIT in metastatic melanoma: ASCO 2009 meeting report. Pigment Cell Melanoma Res. 2009 Aug;22(4):386-387. Pubmedid: 19624312.   Pubmed ID: 19624312

11. Alfano RW, Leppla SH, Liu S, Bugge TH, Herlyn M, Smalley KS, Bromberg-White JL, Duesbery NS, Frankel AE. Cytotoxicity of the matrix metalloproteinase-activated anthrax lethal toxin is dependent on gelatinase expression and B-RAF status in human melanoma cells. Mol Cancer Ther. 2008 May;7(5):1218-1226. Pubmedid: 18483309.   Pubmed ID: 18483309

12. Fong L, Jiang Y, Riley M, Liu X, Smalley K, Guttridge D, Farber J. Prevention of upper aerodigestive tract cancer in zinc-deficient rodents: inefficacy of genetic or pharmacological disruption of COX-2. Int J Cancer. 2008 Mar;122(5):978-989. Pubmedid: 17985342.   Pubmed ID: 17985342

13. Haass NK, Sproesser K, Nguyen TK, Contractor R, Medina CA, Nathanson KL, Herlyn M, Smalley KS. 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. Clin Cancer Res. 2008 Jan;14(1):230-239. Pubmedid: 18172275.   Pubmed ID: 18172275

14. Lioni M, Noma K, Snyder A, Klein-Szanto A, Diehl JA, Rustgi AK, Herlyn M, Smalley KS. Bortezomib induces apoptosis in esophageal squamous cell carcinoma cells through activation of the p38 mitogen-activated protein kinase pathway. Mol Cancer Ther. 2008 Sep;7(9):2866-2875. Pubmedid: 18790767.   Pubmed ID: 18790767

15. Maksimoska J, Williams DS, Atilla-Gokcumen GE, Smalley KS, Carroll PJ, Webster RD, Filippakopoulos P, Knapp S, Herlyn M, Meggers E. Similar biological activities of two isostructural ruthenium and osmium complexes. Chemistry. 2008;14(16):4816-4822. Pubmedid: 18425743.   Pubmed ID: 18425743

16. Noma K, Smalley KS, Lioni M, Naomoto Y, Tanaka N, El-Deiry W, King AJ, Nakagawa H, Herlyn M. The essential role of fibroblasts in esophageal squamous cell carcinoma-induced angiogenesis. Gastroenterology. 2008 Jun;134(7):1981-1993. Pubmedid: 18439605.   Pubmed ID: 18439605

17. Smalley KS, Contractor R, Nguyen TK, Xiao M, Edwards R, Muthusamy V, King AJ, Flaherty KT, Bosenberg M, Herlyn M, Nathanson KL. Identification of a novel subgroup of melanomas with KIT/cyclin-dependent kinase-4 overexpression. Cancer Res. 2008 Jul;68(14):5743-5752. Pubmedid: 18632627.   Pubmed ID: 18632627

18. Smalley KS, Lioni M, Dalla Palma M, Xiao M, Desai B, Egyhazi S, Hansson J, Wu H, King AJ, Van Belle P, Elder DE, Flaherty KT, Herlyn M, Nathanson KL. Increased cyclin D1 expression can mediate BRAF inhibitor resistance in BRAF V600E-mutated melanomas>. Mol Cancer Ther. 2008 Sep;7(9):2876-2883. Pubmedid: 18790768.   Pubmed ID: 18790768

19. Tsai J, Lee JT, Wang W, Zhang J, Cho H, Mamo S, Bremer R, Gillette S, Kong J, Haass NK, Sproesser K, Li L, Smalley KS, Fong D, Zhu YL, Marimuthi A, Nguyen H, Lam B, Liu J, Cheung I, Rice J, Suzuki Y, Luu C, Settachatgul C, Shellooe R, Cantwell J, Kim SH, Schlessinger J, Zhang KY, West BL, Powell B, Habets G, Zhang C, Bollag G, Ibrahim PN, Hirth P, Artis DR, Herlyn M. Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity. Proc Natl Acad Sci U S A. 2008 Feb;105(8):3041-3046. Pubmedid: 18287029.   Pubmed ID: 18287029

20. Xie P, Williams D, Atilla-Gokcumen G, Milk L, Xiao M, Smalley K, Herlyn M, Meggers E, Marmorstein R. Structure-based design of an organoruthenium phosphatidyl-inositol-3 kinase inhibitor reveals a switch governing lipid kinase potency and selectivity. Acs Chem Biol. 2008 May;3(5):305-316. Pubmedid: 18484710.   Pubmed ID: 18484710

21. Lioni M, Brafford P, Andl C, Rustgi A, El-Deiry W, Herlyn M, Smalley KS. Dysregulation of claudin-7 leads to loss of E-cadherin expression and the increased invasion of esophageal squamous cell carcinoma cells. Am J Pathol. 2007 Feb;170(2):709-721. Pubmedid: 17255337.   Pubmed ID: 17255337

22. Lopez-Bergami P, Huang C, Goydos JS, Yip D, Bar-Eli M, Herlyn M, Smalley KS, Mahale A, Eroshkin A, Aaronson S, Ronai Z. Rewired ERK-JNK signaling pathways in melanoma. Cancer Cell. 2007 May;11(5):447-460. Pubmedid: 17482134.   Pubmed ID: 17482134

23. Smalley K, Contractor R, Haass N, Lee J, Nathanson K, Medina C, FlahertyKT, Herlyn M. Ki67 expression levels are a better marker of reduced melanoma growth following MEK inhibitor treatment than phospho-ERK levels. Br J Cancer. 2007 Feb;96(3):445-449. Pubmedid: 17245336.   Pubmed ID: 17245336

24. Smalley KS, Contractor R, Haass NK, Kulp AN, Atilla-Gokcumen GE, Williams DS, Bregman H, Flaherty KT, Soengas MS, Meggers E, Herlyn M. An organometallic protein kinase inhibitor pharmacologically activates p53 and induces apoptosis in human melanoma cells. Cancer Res. 2007 Jan;67(1):209-217. Pubmedid: 17210701.   Pubmed ID: 17210701

25. Smalley KS, Flaherty KT. Is ERK activation a good biomarker for estradiol and tamoxifen effects?. Cancer Biol Ther. 2007 Jan;6(1):119-120. Pubmedid: 17264668.   Pubmed ID: 17264668

26. Fang D, Leishear K, Nguyen T, Finko R, Cai K, Fukunaga M, Li L, Brafford P, Kulp A, Xu X, Smalley K, Herlyn M. Defining the conditions for the generation of melanocytes from human embryonic stem cells. Stem Cells. 2006 Jul;24(7):1668-1677. Pubmedid: 16574754.   Pubmed ID: 16574754

27. King AJ, Patrick DR, Batorsky RS, Ho ML, Do HT, Zhang SY, Kumar R, Rusnak DW, Takle AK, Wilson DM, Hugger E, Wang L, Karreth F, Lougheed JC, Lee J, Chau D, Stout TJ, May EW, Rominger CM, Schaber MD, Luo L, Lakdawala AS, Adams JL, Contractor RG, Smalley KS, Herlyn M, Morrissey MM, Tuveson DA, Huang PS. Demonstration of a genetic therapeutic index for tumors expressing oncogenic BRAF by the kinase inhibitor SB-590885. Cancer Res. 2006 Dec;66(23):11100-11105. Pubmedid: 17145850.   Pubmed ID: 17145850

28. Liu ZJ, Xiao M, Balint K, Smalley KS, Brafford P, Qiu R, Pinnix CC, Li X, Herlyn M. Notch1 signaling promotes primary melanoma progression by activating mitogen-activated protein kinase/phosphatidylinositol 3-kinase-Akt pathways and up-regulating N-cadherin expression. Cancer Res. 2006 Apr;66(8):4182-4190. Pubmedid: 16618740.   Pubmed ID: 16618740

29. Smalley K, Herlyn M. Towards the targeted therapy of melanoma. Mini Rev Med Chem. 2006 Apr;6(4):387-393. Pubmedid: 16613575.   Pubmed ID: 16613575

30. Smalley K, Lioni M, Herlyn M. Life isn't flat: taking cancer biology to the next dimension. In Vitro Cell Dev Biol Anim. 2006 Sep;42(8-9):242-247. Pubmedid: 17163781.   Pubmed ID: 17163781

31. Smalley KS, Haass NK, Brafford PA, Lioni M, Flaherty KT, Herlyn M. Multiple signaling pathways must be targeted to overcome drug resistance in cell lines derived from melanoma metastases. Mol Cancer Ther. 2006 May;5(5):1136-1144. Pubmedid: 16731745.   Pubmed ID: 16731745

32. Haass N, Smalley K, Li L, Herlyn M. Adhesion, migration and communication in melanocytes and melanoma. Pigment Cell Res. 2005 Jun;18(3):150-159. Pubmedid: 15892711.   Pubmed ID: 15892711

33. Meier F, Schittek B, Busch S, Garbe C, Smalley K, Satyamoorthy K, Li G, Herlyn M. The RAS/RAF/MEK/ERK and PI3K/AKT signaling pathways present molecular targets for the effective treatment of advanced melanoma. Front Biosci. 2005 Sep;10:2986-3001. Pubmedid: 15970553.   Pubmed ID: 15970553

34. Smalley K, Brafford P, Herlyn M. Selective evolutionary pressure from the tissue microenvironment drives tumor progression. Semin Cancer Biol. 2005 Dec;15(6):451-459. Pubmedid: 16043361.   Pubmed ID: 16043361

35. Smalley K, Lioni M, Herlyn M. Targeting the stromal fibroblasts: a novel approach to melanoma therapy. Expert Rev Anticancer Ther. 2005 Dec;5(6):1069-1078. Pubmedid: 16336098.   Pubmed ID: 16336098

36. Smalley KS, Brafford P, Haass NK, Brandner JM, Brown E, Herlyn M. Up-regulated expression of zonula occludens protein-1 in human melanom aassociates with N-cadherin and contributes to invasion and adhesion. Am J Pathol. 2005 May;166(5):1541-1554. Pubmedid: 15855653.   Pubmed ID: 15855653

37. Smalley KS, Herlyn M. Targeting intracellular signaling pathways as a novel strategy in melanoma therapeutics. Ann N Y Acad Sci. 2005 Nov;1059:16-25. Pubmedid: 16382039.   Pubmed ID: 16382039

38. Haass N, Smalley K, Herlyn M. The role of altered cell-cell communication in melanoma progression. J Mol Histol. 2004 Mar;35(3):309-318. Pubmedid: 15339050.   Pubmed ID: 15339050

39. Smalley KS, Herlyn M. Loitering with intent: new evidence for the role of BRAF mutations in the proliferation of melanocytic lesions. J Invest Dermatol. 2004 Oct;123(4):xvi-xvii. Pubmedid: 15373800.   Pubmed ID: 15373800

40. Smalley K, Herlyn M. The great escape: another way for melanoma to leave physiological control. J Invest Dermatol. 2003 Oct;121(4):xi-xii. Pubmedid: 14632176.   Pubmed ID: 14632176

41. Smalley KS, Eisen TG. Farnesyl transferase inhibitor SCH66336 is cytostatic, pro-apoptotic and enhances chemosensitivity to cisplatin in melanoma cells. Int J Cancer. 2003 Jun;105(2):165-175. Pubmedid: 12673674.   Pubmed ID: 12673674

42. Smalley KS. A pivotal role for ERK in the oncogenic behaviour of malignant melanoma. Int J Cancer. 2003 May;104(5):527-532. Pubmedid: 12594806.   Pubmed ID: 12594806

43. Smalley K, Eisen T. Differentiation of human melanoma cells through p38 MAP kinase is associated with decreased retinoblastoma protein phosphorylation and cell cycle arrest. Melanoma Res. 2002 Jun;12(3):187-192. Pubmedid: 12140374.   Pubmed ID: 12140374

44. Smalley KS, Eisen TG. Farnesyl thiosalicylic acid inhibits the growth of melanoma cells through a combination of cytostatic and pro-apoptotic effects. Int J Cancer. 2002 Apr;98(4):514-522. Pubmedid: 11920610.   Pubmed ID: 11920610

45. Smalley K, Koenig J, Feniuk W, Humphrey P. Ligand internalization and recycling by human recombinant somatostatin type 4 (hsst(4)) receptors expressed in CHO-K1 cells. Br J Pharmacol. 2001 Mar;132(5):1102-1110. Pubmedid: 11226141.   Pubmed ID: 11226141

46. Stebbing J, Benson C, Eisen T, Pyle L, Smalley K, Bridle H, Mak I, Sapunar F, Ahern R, Gore M. The treatment of advanced renal cell cancer with high-dose oral thalidomide. Br J Cancer. 2001 Sep;85(7):953-958. Pubmedid: 11592764.   Pubmed ID: 11592764

47. Smalley K, Eisen T. The involvement of p38 mitogen-activated protein kinase in the alpha-melanocyte stimulating hormone (alpha-MSH)-induced melanogenic and anti-proliferative effects in B16 murine melanoma cells. Febs Lett. 2000 Jul;476(3):198-202. Pubmedid: 10913613.   Pubmed ID: 10913613

48. Smalley K, Feniuk W, Sellers L, Humphrey P. The pivotal role of phosphoinositide-3 kinase in the human somatostatin sst(4) receptor-mediated stimulation of p44/p42 mitogen-activated protein kinase and extracellular acidification. Biochem Biophys Res Commun. 1999 Sep;263(1):239-243. Pubmedid: 10486283.   Pubmed ID: 10486283

49. Smalley K, Feniuk W, Humphrey P. Differential agonist activity of somatostatin and L-362855 at human recombinant sst4 receptors. Br J Pharmacol. 1998 Oct;125(4):833-841. Pubmedid: 9831922 .   Pubmed ID: 9831922