examining 12-week treatment with 10% or 20% VDA-1102 ointment is ongoing (ClinicalTrials.gov Identifier: NCT03538951).
Treatment options for AKs continue to expand as pharma-ceutical developers aim to improve clinical efficacy and reduce post-treatment downtime. At present, therapies with the highest levels of lesion clearance—such as 5% 5-FU— are inevitably tied to local skin irritation. Daylight PDT has demonstrated encouraging results and may offer comparable efficacy to conventional PDT with only minimal associated pain. In addition, exploring agents with improved tolerability remains an active area of research. Investigational therapies currently in trial development are utilizing novel mechanisms in order to circumvent the limitations of classic modalities.
Dr. Rigel has served as a consultant and advisory board member for LEO Pharma. Dr. Kircik has served either as an investigator, advisory board member, speaker, or consultant for Almirall, LEO Pharma, and Ortho Dermatologics. Dr. Bhatia has served either as an investigator, advisory board member, speaker, or consultant for Allergan, Biofrontera, Dermira, Dusa, Exeltis, Ferndale, ISDIN, LaRoche-Posay, LEO Pharma, PharmaDerm, Regeneron, Sanofi, SunPharma, and Valeant. Dr. Hashim and Tinley Chen have no conficts.
Filosa A, Filosa G. Actinic keratosis and squamous cell carcinoma: clinical and pathological features. G Ital Dermatol Venereol. 2015;150(4):379-84.Lober BA, Lober CW. Actinic keratosis is squamous cell carcinoma. South Med J. 2000;93(7):650-5.Ahn CS, Allen MM, Davis SA, Huang KE, Fleischer AB, Jr., Feldman SR. The National Ambulatory Medical Care Survey: a resource for understanding the outpatient dermatology treatment. J Dermatolog Treat. 2014;25(6):453-8.Bickers DR, Lim HW, Margolis D, Weinstock MA, Goodman C, Faulkner E, et al. The burden of skin diseases: 2004 a joint project of the American Academy of Dermatology Association and the Society for Investigative Dermatology. J Am Acad Dermatol. 2006;55(3):490-500.Cockerell CJ. Histopathology of incipient intraepidermal squamous cell carcinoma ("actinic keratosis"). J Am Acad Dermatol. 2000;42(1 Pt 2):11-7.Frost CA, Green AC. Epidemiology of solar keratoses. Br J Dermatol. 1994;131(4):455-64.Flohil SC, van der Leest RJ, Dowlatshahi EA, Hofman A, de Vries E, Nijsten T. Prevalence of actinic keratosis and its risk factors in the general population: the Rotterdam Study. J Invest Dermatol. 2013;133(8):1971-8.Harvey I, Frankel S, Marks R, Shalom D, Nolan-Farrell M. Non-melanoma skin cancer and solar keratoses. I. Methods and descriptive results of the South Wales Skin Cancer Study. Br J Cancer. 1996;74(8):1302-7.Salasche SJ. Epidemiology of actinic keratoses and squamous cell carcinoma. J Am Acad Dermatol. 2000;42(1 Pt 2):4-7.Lebwohl MG, Rosen T, Stockfleth E. The role of human papillomavirus in common skin conditions: current viewpoints and therapeutic options. Cutis. 2010;86(5):suppl 1-11; quiz suppl 2.Berman B, Cockerell CJ. Pathobiology of actinic keratosis: ultraviolet-dependent keratinocyte proliferation. J Am Acad Dermatol. 2013;68(1 Suppl 1):S10-9.Ratushny V, Gober MD, Hick R, Ridky TW, Seykora JT. From keratinocyte to cancer: the pathogenesis and modeling of cutaneous squamous cell carcinoma. J Clin Invest. 2012;122(2):464-72.Grossman D, Leffell DJ. The molecular basis of nonmelanoma skin cancer: new understanding. Arch Dermatol. 1997;133(10):1263-70.Kanellou P, Zaravinos A, Zioga M, Stratigos A, Baritaki S, Soufla G, et al. Genomic instability, mutations and expression analysis of the tumour suppressor genes p14(ARF), p15(INK4b), p16(INK4a) and p53 in actinic keratosis. Cancer Lett. 2008;264(1):145-61.Brash DE, Rudolph JA, Simon JA, Lin A, McKenna GJ, Baden HP, et al. A role for sunlight in skin cancer: UV-induced p53 mutations in squamous cell carcinoma. Proc Natl Acad Sci USA. 1991;88(22):10124-8.Nelson MA, Einspahr JG, Alberts DS, Balfour CA, Wymer JA, Welch KL, et al. Analysis of the p53 gene in human precancerous actinic keratosis lesions and squamous cell cancers. Cancer Lett. 1994;85(1):23-9.Ziegler A, Jonason AS, Leffell DJ, Simon JA, Sharma HW, Kimmelman J, et al. Sunburn and p53 in the onset of skin cancer. Nature. 1994;372(6508):773-6.Jiang W, Ananthaswamy HN, Muller HK, Kripke ML. p53 protects against skin cancer induction by UV-B radiation. Oncogene. 1999;18(29):4247-53.Marks R, Foley P, Goodman G, Hage BH, Selwood TS. Spontaneous remission of solar keratoses: the case for conservative management. Br J Dermatol. 1986;115(6):649-55.Marks R, Rennie G, Selwood TS. Malignant transformation of solar keratoses to squamous cell carcinoma. Lancet. 1988;1(8589):795-7.Glogau RG. The risk of progression to invasive disease. J Am Acad Dermatol. 2000;42(1 Pt 2):23-4.Fuchs A, Marmur E. The kinetics of skin cancer: progression of actinic keratosis to squamous cell carcinoma. Dermatol Surg. 2007;33(9):1099-101.Jiyad Z, Marquart L, O'Rourke P, Green AC. The natural history of actinic keratoses in organ transplant recipients. J Am Acad Dermatol. 2017;76(1):162-4.Mittelbronn MA, Mullins DL, Ramos-Caro FA, Flowers FP. Frequency of pre-existing actinic keratosis in cutaneous squamous cell carcinoma. Int J Dermatol. 1998;37(9):677-81.Guenthner ST, Hurwitz RM, Buckel LJ, Gray HR. Cutaneous squamous cell carcinomas consistently show histologic evidence of in situ changes: a clinicopathologic correlation. J Am Acad Dermatol. 1999;41(3 Pt 1):443-8.Quaedvlieg PJ, Tirsi E, Thissen MR, Krekels GA. Actinic keratosis: how to differentiate the good from the bad ones? Eur J Dermatol. 2006;16(4):335-9.Marks VJ. Actinic keratosis. A premalignant skin lesion. Otolaryngol Clin North Am. 1993;26(1):23-35.Neville JA, Welch E, Leffell DJ. Management of nonmelanoma skin cancer in 2007. Nat Clin Pract Oncol. 2007;4(8):462-9.Thai KE, Fergin P, Freeman M, Vinciullo C, Francis D, Spelman L, et al. A prospective study of the use of cryosurgery for the treatment of actinic keratoses. Int J Dermatol. 2004;43(9):687-92.Winton GB, Salasche SJ. Dermabrasion of the scalp as a treatment for actinic damage. J Am Acad Dermatol. 1986;14(4):661-8.Coleman WP, 3rd, Yarborough JM, Mandy SH. Dermabrasion for prophylaxis and treatment of actinic keratoses. Dermatol Surg. 1996;22(1):17-21.Wan MT, Lin JY. Current evidence and applications of photodynamic therapy in dermatology. Clin Cosmet Investig Dermatol. 2014;7:145-63.Pariser DM, Houlihan A, Ferdon MB, Berg JE, Group P-AI. Randomized vehicle-controlled study of short drug incubation aminolevulinic acid photodynamic therapy for actinic keratoses of the face or scalp. Dermatol Surg. 2016;42(3):296-304.Philipp-Dormston WG, Karrer S, Petering H, Ulrich C, Dirschka T, Berking C, et al. Daylight PDT with MAL-current data and practical recommendations of an expert panel. J Dtsch Dermatol Ges. 2015;13(12):1240-9.Lacour JP, Ulrich C, Gilaberte Y, Von Felbert V, Basset-Seguin N, Dreno B, et al. Daylight photodynamic therapy with methyl aminolevulinate cream is effective and nearly painless in treating actinic keratoses: a randomised, investigator-blinded, controlled, phase III study throughout Europe. J Eur Acad Dermatol Venereol. 2015;29(12):2342-8.Rubel DM, Spelman L, Murrell DF, See JA, Hewitt D, Foley P, et al. Daylight photodynamic therapy with methyl aminolevulinate cream as a convenient, similarly effective, nearly painless alternative to conventional photodynamic therapy in actinic keratosis treatment: a randomized controlled trial. Br J Dermatol. 2014;171(5):1164-71.Schon MP, Schon M. Imiquimod: mode of action. Br J Dermatol. 2007;157 Suppl 2:8-13.Hadley G, Derry S, Moore RA. Imiquimod for actinic keratosis: systematic review and meta-analysis. J Invest Dermatol. 2006;126(6):1251-5.Swanson N, Abramovits W, Berman B, Kulp J, Rigel DS, Levy S. Imiquimod 2.5% and 3.75% for the treatment of actinic keratoses: results of two placebo-controlled studies of daily application to the face and balding scalp for two 2-week cycles. J Am Acad Dermatol. 2010;62(4):582-90.Maltusch A, Rowert-Huber J, Matthies C, Lange-Asschenfeldt S, Stockfleth E. Modes of action of diclofenac 3%/hyaluronic acid 2.5% in the treatment of actinic keratosis. J Dtsch Dermatol Ges. 2011;9(12):1011-7.Pirard D, Vereecken P, Melot C, Heenen M. Three percent diclofenac in 2.5% hyaluronan gel in the treatment of actinic keratoses: a meta-analysis of the recent studies. Arch Dermatol Res. 2005;297(5):185-9.Smith SR, Morhenn VB, Piacquadio DJ. Bilateral comparison of the efficacy and tolerability of 3% diclofenac sodium gel and 5% 5-fluorouracil cream in the treatment of actinic keratoses of the face and scalp. J Drugs Dermatol. 2006;5(2):156-9.Rosen RH, Gupta AK, Tyring SK. Dual mechanism of action of ingenol mebutate gel for topical treatment of actinic keratoses: rapid lesion necrosis followed by lesion-specific immune response. J Am Acad Dermatol. 2012;66(3):486-93.Lebwohl M, Swanson N, Anderson LL, Melgaard A, Xu Z, Berman B. Ingenol mebutate gel for actinic keratosis. N Engl J Med. 2012;366(11):1010-9.Eaglstein WH, Weinstein GD, Frost P. Fluorouracil: mechanism of action in human skin and actinic keratoses. I. Effect on DNA synthesis in vivo. Arch Dermatol. 1970;101(2):132-9.Askew DA, Mickan SM, Soyer HP, Wilkinson D. Effectiveness of 5-fluorouracil treatment for actinic keratosis--a systematic review of randomized controlled trials. Int J Dermatol. 2009;48(5):453-63.Gupta AK, Paquet M. Network meta-analysis of the outcome 'participant complete clearance' in nonimmunosuppressed participants of eight interventions for actinic keratosis: a follow-up on a Cochrane review. Br J Dermatol. 2013;169(2):250-9.Smolinski MP, Bu Y, Clements J, Gelman IH, Hegab T, Cutler DL, et al. Discovery of novel dual mechanism of action src signaling and tubulin polymerization inhibitors (KX2-391 and KX2-361). J Med Chem. 2018;61(11):4704-19.Jarratt M KS, Forman S, Cutler D, Wang Hui, Fang Jane, Kwan R, editor Phase II Study of KX2-391 Ointment 1%, a Novel Field Treatment Based on Src/Tubulin Polymerization Inhibition, for Actinic Keratosis. AAD Annual Meeting; 2018; San Diego, CA.Yang CC, Wong TW, Lee CH, Hong CH, Chang CH, Lai FJ, et al. Efficacy and safety of topical SR-T100 gel in treating actinic keratosis in Taiwan: a phase III randomized double-blind vehicle-controlled parallel trial. J Dermatol Sci. 2018;90(3):295-302.
Leon H. Kircik MD email@example.com