Evolution of Clinical and Molecular Responses to Bexarotene Treatment in Cutaneous T-Cell Lymphoma

Abstract

Background: The mechanisms of action of bexarotene are not well understood. Methods: A retrospective study on patients with cutaneous T-cell lymphoma (CTCL) treated with bexarotene was performed to see if bexarotene could act on the dominant T-cell clones. Thirty-five patients were included. Twenty-three were treated with bexarotene for more than 3 months (300 mg/m²). In 7 patients, phototherapy was given with bexarotene. Results: Dominant T-cell clones were observed in 11 patients in peripheral blood and in 19 patients in skin. Our results demonstrate no significant evolution of T-cell clones either in skin or peripheral blood. Furthermore, the detection of T-cell clones in peripheral blood before starting bexarotene was significantly associated with the progression of the disease. UV therapy given with bexarotene significantly improved therapeutic response without any correlation with T-cell clones. Conclusion: This is the first study on the evolution of the T-cell clone in blood and skin in CTCL patients during bexarotene therapy.

Oligodendrocyte regeneration: Its significance in myelin replacement and neuroprotection in multiple sclerosis

“…Further, knockdown of RXR-γ receptor by RNA interference/RXR-specific antagonists dramatically reduces OPC differentiation in vitro and RXR-γ knockout mice exhibit significantly less mature oligodendrocytes following demyelination (Huang et al, 2011). These studies suggest that RXR-γ signaling may regulate oligodendrocyte differentiation and open new doors for pharmacological targeting using RXR ligands, many of which are under study or already approved for the treatment of certain cancers (Ballanger et al, 2010). …”

Neuroprotection and repair in multiple sclerosis

“…121 Bexarotene, a licensed RXR agonist, is already in clinical use for the treatment of cutaneous T-cell lymphoma. 122 RXR agonists are known to be able to attenuate inflammation by regulating macrophage activity. 123,124 Moreover, bexarotene was shown to enhance the clearance of soluble amyloid-β (Aβ), resulting in a significant reduction of Aβ plaques in a mouse model of Alzheimer disease, 125 which suggests that the drug could mediate enhanced phagocytic clearance of remyelination-inhibitory myelin debris.…”

Remyelinating strategies in multiple sclerosis

“…The RXR agonist bexarotene has been approved for all stages of cutaneous T-cell lymphoma [150]. Furthermore, the administration of bexarotene in a mouse model of Alzheimer's disease enhanced the clearance of soluble b-amyloid, leading to a significant reduction of b-amyloid plaques [151], pointing to the capacity of the drug to mediate enhanced phagocytic clearance of remyelination-inhibitory myelin debris [152].…”