Oral retinoids and rexinoids in cutaneous T-cell lymphomas

Abstract

Retinoids are biologically active derivatives of vitamin A modulating cell proliferation, differentiation, apoptosis and altering the immune response. They have been used for years in therapy of cutaneous T-cell lymphomas (CTCL) but the exact mechanism of retinoids’ action is unclear. It is based on the presence of specific receptors’ families, mediating the biological effects of retinoids on the tumor cells: retinoic acid receptor (RAR) and retinoic X receptor (RXR). Orally administrated bexarotene, the first synthetic selective RXR retinoid, was revealed to be active against the cutaneous manifestation of CTCL. The toxicity profile caused by bexarotene seems to be more limited to laboratory values and better tolerated than classical retinoids, but generally associated with more severe grades of toxicity. Both selective retinoic acid receptor- and retinoic X receptor-mediated retinoids have modest objective response rates and, therefore, most likely will have limited impact as monotherapeutic agents. However, the immunomodulatory effects of RAR and RXR retinoids provide a rational basis for using retinoids in combination with other biologic immune response modifiers, phototherapy and radiotherapy. The authors reviewed the literature on the results of the use of retinoids and rexinoids in patients with mycosis fungoides and Sézary syndrome.

The Role of Systemic Retinoids in the Treatment of Cutaneous T-Cell Lymphoma

“…1 Transactivation of some of these other nuclear receptors is believed to be linked to some of the side effects seen with the retinoids. 1 Despite significant progress in elucidating the mechanism by which retinoids exert their activity, their effect on tumorigenesis and cancer biology remains poorly understood. The RAR receptors bind only to all-trans retinoid acid, 9-cis retinoic acid or synthetic isotretinoin, etretinate, and acitretin.…”

“…Each receptor is associated with 3 subtypes, a, b, and, g, which bind to specific ligands. 1,14 These receptors are part of a larger superfamily of nuclear receptors, including thyroid hormone receptor, vitamin D3 receptor, and glucocorticoid receptor ( Table 1). 1 Transactivation of some of these other nuclear receptors is believed to be linked to some of the side effects seen with the retinoids.…”

“…1,14 These receptors are part of a larger superfamily of nuclear receptors, including thyroid hormone receptor, vitamin D3 receptor, and glucocorticoid receptor ( Table 1). 1 Transactivation of some of these other nuclear receptors is believed to be linked to some of the side effects seen with the retinoids. 1 Despite significant progress in elucidating the mechanism by which retinoids exert their activity, their effect on tumorigenesis and cancer biology remains poorly understood.…”

“…Retinoid receptors are found ubiquitously in virtually all organ systems, and they regulate important functions in the body, including embryonic development, vision, immune and neural function, as well as cell proliferation, differentiation, and apoptosis. 1,2 These compounds exert their effects through control of gene expression. In the treatment of cancer, the retinoids are considered "biologic response modifiers" (BRMs) in that they are dissimilar to traditional cytotoxic chemotherapy, inducing response without immune suppression, and often augmenting the immune response.…”

Targeting truncated RXRα for cancer therapy

“…The mechanism of Targretin action has yet to be fully elucidated. It has been shown that the drug can induce apoptosis, differentiation and cellular senescence, inhibit metastasis and angiogenesis, and block cell cycle progression, which was reviewed recently [73][74][75][76].…”