Isotretinoin is a promising agent for glioblastoma. 13-cis-Retinoic acid (cRA) is a synthetic analog of vitamin A, which binds to all three subtypes of retinoic acid receptors (RARα, β, and γ) and retinoid X receptors (RXRα, β, and γ). RAR and RXR are members of the nuclear steroid receptor family, bind as homodimers or heterodimers to specific DNA response elements, and influence the transcription of relevant genes. Retinoids have diverse biologic effects in malignant conditions, including regulating the synthesis of enzymes, growth factors, and binding proteins. Retinoids also modulate genomic and postgenomic expression, exert antiangiogenic effects, and interact with protein kinase-C pathways. The retinoic acid receptor and its ligand mediate trans- repression of activating-protein-1, which is a heterodimeric transcription factor composed of fos- and jun-related proteins. Retinoids also protect the regulatory domain of protein kinase-C from modification induced by oxidant tumor promoters. In hematologic and nonhematologic (skin and head and neck) tumors, treatment with retinoids has demonstrated some efficacy. A phase 2 pilot study of cRA given to patients with progressive or recurrent glioma after failing radiation and conventional chemotherapy demonstrated encouraging results in 1996 and 1999 (Yung et al). Since then, other reports were published. It is not to the point of being combined with various other active drugs in phase II studies.
Siew-Ju See, Victor A. Levin, W.-K. Alfred Yung, Kenneth R. Hess, and Morris D. Groves
13-cis-Retinoic acid in the treatment of recurrent glioblastoma multiforme Neuro-oncol. 2004 July; 6(3): 253–258.
Yung WK, Kyritsis AP, Gleason MJ, Levin VA.Treatment of recurrent malignant gliomas with high-dose 13-cis-retinoic acid. Clin Cancer Res. 1996 Dec;2(12):1931-5.