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COX-2 is a novel target in therapy of mycosis fungoides

Leukemia volume 24, pages 2127–2129 (2010)Cite this article

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Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma (CTCL), a heterogeneous group of lymphocytic neoplasms affecting the skin. Early disease is characterized by skin patches or plaques that are based mostly on infiltrates of reactive inflammatory cells with rare malignant T cells present in the affected areas. In advanced-stage disease, that is tumor stages, however, the malignant clone expands and predominates the skin lesion; moreover, it can spread to lymph nodes, blood and eventually viscera.1 MF is considered an incurable condition, however, due to its indolent nature, early-stage disease can be controlled for years by skin-directed therapies, such as topical corticosteroids, narrow band ultraviolet B or ultraviolet A in combination with psoralen (PUVA), and nitrogen mustard. If the disease becomes refractory to these measures, retinoids/rexinoids, interferon α, histone deacetylase (HDAC) inhibitors and low-dose chemotherapy can be used alone or in combination. Side effects accompanying these therapies range from drug hypersensitivity to increase in the risk of infection or secondary cancer, hematologic toxicity and myelosuppression. Treatment of advanced disease is problematic and often requires aggressive chemotherapy, irradiation or multiple target approaches with responses that are typically not durable; thus, the patients have a poor prognosis. Accordingly, there is a great need to develop novel targeted therapies and combination therapy for the treatment of refractory and advanced MF.2

The etiology of MF is largely unknown, but numerous signaling pathways have been demonstrated to be involved in disease development and progression. A pathological dysregulation of the janus kinase (Jak)/signal transducer and activators of transcription (Stat) signaling axis has been detected in the majority of patients as well as a constitutive activation of other transcription factors such as NF-κB, c-Fos, c-Jun or c-Myc. Abnormal expression of cytokines interleukin (IL)-5, IL-6, IL-7, and IL-13 and angiogenetic factors is also a characteristic feature of MF.3, 1 Recently, we discovered that cyclooxygenase-2 (COX-2) is aberrantly expressed in situ in advanced MF. Importantly, the aberrant COX-2 expression is associated with disease progression suggesting a role in the malignant transformation.4 In normal cells, COX-2 is an inducible key factor in prostaglandin synthesis and mediates inflammation by increased levels of prostaglandin. Ectopic expression of COX-2 and its downstream partner microsomal prostaglandin E synthase-1 (mPGES1) has been implicated in the pathogenesis of several cancer types, and the resulting production of prostaglandin E2 (PGE2) is known to sustain cancer progression by promotion of angiogenesis, invasion and metastasis.5, 6 In advanced MF, the aberrant COX-2 drives a spontaneous, high production of PGE2. In this respect it is important to note that PGE2 functions as growth factor for malignant T cells, and inhibitors of COX-2 and mPGES1 strongly inhibit PGE2-mediated proliferation of malignant T cells.4 In particular, a COX-2 inhibitor already in clinical use for inflammatory diseases, celecoxib (Celebra, Pfizer, Ballerup, Denmark), is a highly potent inhibitor of the spontaneous proliferation of malignant T cells in vitro.4

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References

  1. Diamandidou E, Cohen PR, Kurzrock R . Mycosis fungoides and Sézary syndrome. Blood 1996; 88: 2385–2409.

    CAS  Google Scholar 

  2. Prince HM, Whittaker S, Hoppe RT . How I treat mycosis fungoides and Sézary syndrome. Blood 2009; 114: 4337–4353.

    Article  CAS  Google Scholar 

  3. Hwang ST, Janik JE, Jaffe ES, Wilson WH . Mycosis fungoides and Sézary syndrome. Lancet 2009; 371: 945–957.

    Article  Google Scholar 

  4. Kopp KLM, Kauczok CS, Lauenborg B, Krejsgaard T, Eriksen KW, Zhang Q et al. COX-2-dependent PGE2 acts as growth factor in mycosis fungoides (MF). Leukemia 2010; 24: 1179–1185.

    Article  CAS  Google Scholar 

  5. Harris RE . Cyclooxygenase-2 (COX-2) and the inflammogenesis of cancer. Subcell Biochem 2007; 42: 93–126.

    Article  Google Scholar 

  6. Greenhough A, Smartt HJ, Moore AE, Roberts HR, Williams AC, Paraskeva C et al. The COX-2/PGE2 pathway: keyroles in the hallmarks of cancer and adaptation to the tumor microenvironment. Carcinogenesis 2009; 30: 377–386.

    Article  CAS  Google Scholar 

  7. Krejsgaard T, Kopp K, Ralfkiaer E, Willumsgaard AE, Eriksen KW, Labuda T et al. A novel xenograft model of cutaneous T-cell lymphoma. Exp Dermatol 2010. doi:10.1111/j.1600-0625.2010.01138.x.

    Article  Google Scholar 

  8. Harris RE . Cyclooxygenase-2 (COX-2) blockade in the chemoprevention of cancers of the colon, breast, prostate, and lung. Inflammopharmacology 2009; 17: 55–67.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Biology, University of Copenhagen, Copenhagen, Denmark

    K L M Kopp, T Krejsgaard, N Ødum & A Woetmann

  2. Institute of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark

    K L M Kopp, T Krejsgaard, K W Eriksen, C Geisler, N Ødum & A Woetmann

  3. Department of Oral Pathology and Medicine, Faculty of Health Sciences, Dental School, University of Copenhagen, Copenhagen, Denmark

    S Dabelsteen

  4. Department of General Dermatology, Medical University of Graz, Graz, Austria

    J C Becker

  5. Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA

    M Wasik

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  1. K L M Kopp
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Correspondence to A Woetmann.

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Kopp, K., Dabelsteen, S., Krejsgaard, T. et al. COX-2 is a novel target in therapy of mycosis fungoides. Leukemia 24, 2127–2129 (2010). https://doi.org/10.1038/leu.2010.221

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