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Journal of Molecular and Clinical Medicine   2019, Vol. 2 Issue (2): 23-28    DOI: 10.31083/j.jmcm.2019.02.9161
Original Research | Next articles
Retinoids offer new and promising cancer therapeutic avenues
Xin Cao1, Quanlin An1, Yehuda G. Assaraf2, *(), Xiangdong Wang1, *()
1 Zhongshan Hospital Institute of Clinical Science, Fudan University Shanghai Medical College, Shanghai 200032, P. R. China
2 The Fred Wyszkowski Cancer Research Lab, Faculty of Biology, Technion-Israel Institute of Technology, Haifa 3200000, Israel
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All trans-retinoic acid (ATRA) as well as several key retinoids including tamibarotene, acyclic retinoid (ACR), and WYC-209, have made a major progress in both pre-clinical cancer therapeutics as well as in the clinical setting regarding the treatment of leukemia and solid tumors via their important impacts on cancer stem cell differentiation or apoptosis. ATRA exerts its antitumor activity by binding to retinoic acid receptors, which in turn specifically bind to DNA as a heterodimer with the retinoid X receptors, at promoter regions known as retinoic acid response elements. The impressive new studies and clinical achievements with retinoids as key pre-clinical research tools and antitumor agents, are summarized and discussed in the current paper. The ongoing clinical trial of tamibarotene, which is the first agent targeting super-enhancers-containing cancers, could provide a new treatment modality for acute myeloid leukemia patients. A recent clinical study for evaluation of the preventive effects of ACR on second primary hepatocellular carcinoma (HCC) demonstrated that the oral administration of ACR for 12 months, significantly reduced HCC recurrence. WYC-209 strongly inhibited cell proliferation of different tumor repopulating cells (TRCs), a highly tumorigenic subpopulation of mouse melanoma cells, and also blocked > 80% of B16 TRCs' lung metastases in wild-type C57BL/6 mice, without any apparent toxicity. These remarkable findings reveal that retinoids constitute a promising class of antitumor agents for the treatment of both hematological malignancies and solid tumors.

Key words:  Retinoids      cancer therapy      cancer stem cells      differentiation      apoptosis     
Published:  20 April 2019     
*Corresponding Author(s):  Yehuda G. Assaraf; Xiangdong Wang     E-mail:;

Cite this article: 

Xin Cao, Quanlin An, Yehuda G. Assaraf, Xiangdong Wang. Retinoids offer new and promising cancer therapeutic avenues. Journal of Molecular and Clinical Medicine , 2019, 2(2): 23-28.

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Figure 1.  Vitamin A metabolic pathway and important retinoids in advanced cancer research and therapy. Vitamin A is converted to retinal via oxidation by retinol dehydrogenases; while retinal is converted to ATRA via further oxidation by retinaldehyde dehydrogenases. The important retinoids in advanced cancer research and therapy include ATRA, tamibarotene, acyclic retinoid, and WYC-209.

Table 1.  Retinoids in recent cancer treatments and advanced cancer research
Retinoids Company Targets Stage Cancer Indications Side effects
Triax Pharm, etc pan-RAR/RXR
Launched Acute promyelocytic leukemia (APL) Liver dysfunction, heart rhythm abnormalities, intestinal toxicity, etc [6, 7]
Tamibarotene Nippon Shinyaku,
Syros Pharma
RARα/β agonist Launched;
Phase II,
NCT02807558 (US)
Recurrent acute promyelocytic leukemia (APL)
Acute Myeloid Leukemia (AML)
Side effects were similar but milder than those of ATRA [8, 9]
(Acyclic retinoid)
Kowa Pharm pan-RAR/RXR
Phase III, NCT01640808 (US) Hepatic Neoplasm Malignant Recurrent Side effects were similar but milder than those of ATRA [10, 11]
WYC-209 Baiyu Pharm RAR modulator Pre-clinical Melanoma metastases, hepatocellular carcinoma (HCC) Unclear [12]
Figure 2.  The docking mode of WYC-209 on RARβ (PDB:1XAP, Gold Suite 5.0). The double H-bonds formed between the oxygen atoms of the carboxyl group of WYC-209 and Arg269/Ser280 of RARβ, may play key roles in functional modulation of RARα/β activity.

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