Molecular markers associated with clinical response to bexarotene therapy in cutaneous T-cell lymphoma.

Abstract	Bexarotene (Targretin(®)), was registered for the treatment of cutaneous T-cell lymphoma (CTCL) in 2002, and has been reported to induce a 45% overall response. Responses are mostly partial or generate a stable, skin-restricted disease. This study explored the usefulness of a novel cancer-associated gene, NAV3 and corresponding chromosome 12 copy numbers as possible biomarkers to monitor the therapeutic response to bexarotene in 21 Finnish patients with CTCL. Six patients (29%) reached complete remission (CR) and 3 of these remained in CR for more than 24 months, 12 (57%) reached a partial response (PR, with one stable disease) and 3 were non-responders. Low-level NAV3 deletions were detected using a fluorescence in-situ hybridization (FISH) assay in the lesions of 5 patients, 4 of whom were non-responders or progressed after short PR. This occurrence of NAV3 deletions was statistically significant compared with non-progressors (p = 0.011, Fisher's exact test). Chromosome 12 tetraploidy was found in the lesions of two of the 3 patients with CR who remained in remission. While such tetraploidy is a feature of proliferating normal T cells, this observation may reflect a favourable anti-tumour immune response among the skin-infiltrating lymphocytes.
Authors	Annamari Ranki, Liisa Väkevä, Laura Sipilä, Kai Krohn
Journal	Acta dermato-venereologica (Acta Derm Venereol) Vol. 91 Issue 5 Pg. 568-73 (Sep 2011) ISSN: 1651-2057 [Electronic] Sweden
PMID	21547336 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Antineoplastic Agents Biomarkers, Tumor Membrane Proteins NAV3 protein, human Nerve Tissue Proteins Tetrahydronaphthalenes Bexarotene
Topics	Antineoplastic Agents (therapeutic use) Bexarotene Biomarkers, Tumor (genetics) Cells, Cultured Chromosomes, Human, Pair 12 Finland Gene Deletion Gene Dosage Humans In Situ Hybridization, Fluorescence Lymphoma, T-Cell, Cutaneous (drug therapy, genetics, immunology) Membrane Proteins (genetics) Nerve Tissue Proteins (genetics) Patient Selection Pharmacogenetics Precision Medicine Remission Induction Skin Neoplasms (drug therapy, genetics, pathology) Tetrahydronaphthalenes (therapeutic use) Tetraploidy Time Factors Treatment Outcome

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