Traffic lights for retinoids in oncology: molecular markers of retinoid resistance and sensitivity and their use in the management of cancer differentiation therapy

Abstract

For decades, retinoids and their synthetic derivatives have been well established anticancer treatments due to their ability to regulate cell growth and induce cell differentiation and apoptosis. Many studies have reported the promising role of retinoids in attaining better outcomes for adult or pediatric patients suffering from several types of cancer, especially acute myeloid leukemia and neuroblastoma. However, even this promising differentiation therapy has some limitations: retinoid toxicity and intrinsic or acquired resistance have been observed in many patients. Therefore, the identification of molecular markers that predict the therapeutic response to retinoid treatment is undoubtedly important for retinoid use in clinical practice. The purpose of this review is to summarize the current knowledge on candidate markers, including both genetic alterations and protein markers, for retinoid resistance and sensitivity in human malignancies.

Suppressing the metastatic properties of the breast cancer cells using STAT3 decoy oligodeoxynucleotides: A promising approach for eradication of cancer cells by differentiation therapy

“…In this regard, targeting tumor‐initiating cells (i.e., CSCs) by novel methods, which promotes BCSCs into differentiated cancer cells, would be a promising avenue for successful treatment. Differentiation therapy, which is able to irreversibly changing the phenotype of the cancer cells, can be tried to reactivate the differentiation process and subsequently eradicate the tumor with minimum damage to the normal adjacent cells (Dobrotkova, Chlapek, Mazanek, Sterba, & Veselska, ).…”

All-Trans Retinoic Acid induces synaptic plasticity in human cortical neurons

“…Vitamin A (all-trans retinol) and its metabolites have recently been linked to physiological brain functions such as axonal sprouting, synaptic plasticity and modulation of cortical activity (Drager, 2006;Shearer et al, 2012). Specifically, all-trans retinoic acid (atRA), which is clinically used in dermatology and oncology (Dobrotkova et al, 2018;Hu et al, 2009), has been studied for its neuroprotective and plasticity-promoting effects in animal models (Chen et al, 2014;Koryakina et al, 2009). Indeed, studies have been initiated that evaluate the effects of atRA in patients with brain diseases associated with cognitive dysfunction, e.g., Alzheimer's disease, Fragile X syndrome, and depression (Bremner et al, 2012;Ding et al, 2008;Zhang et al, 2018).…”

Prediction of neuroblastoma cell response to treatment with natural or synthetic retinoids using selected protein biomarkers

“…Although retinoids as differentiation inducers represent an important part of high-risk NBL treatment, their toxicity and acquired resistance to retinoids limit their use in clinical practice [5]. Therefore, identifying molecular markers that can predict the therapeutic response to retinoids is an important aspect for their use in clinical practice [6].…”

“…Although the administration of retinoids represents an important part of treatment for children suffering from high-risk NBL, approximately 50% of these patients do not respond to this therapy or develop resistance to retinoids during treatment [5]. The present study focused on the comparative analysis of the expression of genes and corresponding proteins (DDX39A, HMGA1, HMGA2, HOXC9 and PBX1) that have recently been discussed as possible predictive biomarkers of the clinical response to retinoid differentiation therapy [6].…”