1066 Case Reports DOI: 10.1111/j.1610-0387.2008.06861.x JDDG | 12 ˙ 2008 (Band 6) © The Authors • Journal compilation © Blackwell Verlag GmbH, Berlin • JDDG • 1610-0379/2008/0612 Summary Cutaneous squamous cell carcinoma (SCC) is one of the most common can- cers worldwide. Epidermal growth factor receptor (EGFR) is expressed at the cell surface by more than 90 % of SCCs and its activation is responsible for cell cycle progression, prolifera- tion, survival, angiogenesis and meta- stasis. Cyclooxygenase-2 (COX-2) is an enzyme up-regulated through EGFR signaling and responsible for some of the EGFR-dependent biological ef- fects. An 88-year-old man presented with a recurrent, locoregionally meta- static SCC of the right parietal region, which was resistant to radiotherapy. With a combination therapy of an EGFR blocker (cetuximab) and a COX- 2 inhibitor (celecoxib), the tumor re- gressed partially and the patient’s Karnofsky index improved. We specu- late that the combined use of cetuxi- mab and COX-2 inhibitors can be a new and effective therapy for advan- ced and recurrent cutaneous SCCs. Keywords squamous cell carcinoma – EGFR – COX-2 – Cetuximab metastatic spread – systemic mono- and multiagent chemotherapy [1]. Few ther- apeutic options are left for advanced or metastatic disease, primarily platinum- containing chemotherapeutic regimens. Advanced SCC often occurs in elderly patients who tolerate systemic chemotherapy poorly; there is a great need for more specifically targeted and safer therapeutic strategies. Almost all cutaneous SCC express EGFR, which may confer metastatic potential [2]. Stimulation of EGFR by its ligands increases signal transduction leading to activation of genes responsible for the biological effects of EGFR (Figure 1 and [3]). Among the genes with increased expression after EGFR stimulation is cyclooxygenase-2 (COX-2) [4]. COX-2 is responsible for production of prostaglandin E2 (PGE2), which is known to rapidly phosphorylate EGFR and to trigger the MAPK signaling path- way [5]. Pai et al. have demonstrated that the inhibition of matrix metallopro- teinases (MMPs), TGF- or c-Src can block PGE2-mediated EGFR transacti- vation and downstream signaling. This indicates that PGE2-induced EGFR transactivation involves signaling trans- duced via TGF-, an EGFR ligand, probably released from the cell membrane by c-Src-activated MMP(s) (Figure 1 and [6]). Thus, up-regulation of COX-2 expression by EGFR stimula- tion may establish a vicious cycle (Figure 1) of increased cell proliferation and incomplete cell differentiation. Indeed, Introduction Cutaneous squamous cell carcinoma SCC is the second most common cancer in whites [1]. In certain clinical settings such as the use of immunosuppressive medications in organ transplant recipi- ents, the risk of developing SCC is increased by 65- to 250-fold [1]. SCCs can be treated either surgically or non- surgically. Non-surgical options include laser, cryotherapy, topical chemotherapy, topical immune response modifiers (e. g. imiquimod), photodynamic therapy (PDT), radiation therapy, and – after Combination of an EGFR blocker and a COX-2 inhibitor for the treatment of advanced cutaneous squamous cell carcinoma Ahmad Jalili, Alice Pinc, Friederike Pieczkowski, Franz M. Karlhofer, Georg Stingl, Stephan N. Wagner Division of Immunology, Allergy and Infectious Diseases (DIAID), Department of Dermatology, Medical University of Vienna JDDG; 2008 • 6:1066–1069 Submitted: 10. 6. 2008 | Accepted: 15. 7. 2008 Figure 1: Schematic presentation of the signaling pathways activated by the EGFR stimulation and their biological relevance.