TY - JOUR
T1 - Molecular pathways
T2 - Current role and future directions of the retinoic acid pathway in cancer prevention and treatment
AU - Connolly, Roisin M.
AU - Nguyen, Nguyen K.
AU - Sukumar, Saraswati
PY - 2013/4/1
Y1 - 2013/4/1
N2 - Retinoids and their naturally metabolized and synthetic products (e.g., all-trans retinoic acid, 13-cis retinoic acid, bexarotene) induce differentiation in various cell types. Retinoids exert their actions mainly through binding to the nuclear retinoic acid receptors (a , b, g ), which are transcriptional and homeostatic regulators with functions that are often compromised early in neoplastic transformation. The retinoids have been investigated extensively for their use in cancer prevention and treatment. Success has been achieved with their use in the treatment of subtypes of leukemia harboring chromosomal translocations. Promising results have been observed in the breast cancer prevention setting, where fenretinide prevention trials have provided a strong rationale for further investigation in young women at high risk for breast cancer. Ongoing phase III randomized trials investigating retinoids in combination with chemotherapy in non-small cell lung cancer aim to definitively characterize the role of retinoids in this tumor type. The limited treatment success observed to date in the prevention and treatment of solid tumors may relate to the frequent epigenetic silencing of RARb. Robust evaluation of RARb and downstream genes may permit optimized use of retinoids in the solid tumor arena.
AB - Retinoids and their naturally metabolized and synthetic products (e.g., all-trans retinoic acid, 13-cis retinoic acid, bexarotene) induce differentiation in various cell types. Retinoids exert their actions mainly through binding to the nuclear retinoic acid receptors (a , b, g ), which are transcriptional and homeostatic regulators with functions that are often compromised early in neoplastic transformation. The retinoids have been investigated extensively for their use in cancer prevention and treatment. Success has been achieved with their use in the treatment of subtypes of leukemia harboring chromosomal translocations. Promising results have been observed in the breast cancer prevention setting, where fenretinide prevention trials have provided a strong rationale for further investigation in young women at high risk for breast cancer. Ongoing phase III randomized trials investigating retinoids in combination with chemotherapy in non-small cell lung cancer aim to definitively characterize the role of retinoids in this tumor type. The limited treatment success observed to date in the prevention and treatment of solid tumors may relate to the frequent epigenetic silencing of RARb. Robust evaluation of RARb and downstream genes may permit optimized use of retinoids in the solid tumor arena.
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U2 - 10.1158/1078-0432.CCR-12-3175
DO - 10.1158/1078-0432.CCR-12-3175
M3 - Review article
C2 - 23322901
AN - SCOPUS:84877091761
SN - 1078-0432
VL - 19
SP - 1651
EP - 1959
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 7
ER -