Retinoic Acid Receptors in Acute Myeloid Leukemia Therapy

Martino, Orsola di; Welch, John S.

doi:10.3390/cancers11121915

Cited by 54 publications

(50 citation statements)

References 113 publications

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“…All-trans retinoic acid (ATRA), the active metabolite of vitamin A, is used in the treatment of acute promyelocytic leukemia, with remarkable results [1,2]. ATRA is a non-conventional anti-tumor drug, being the first example of a cyto-differentiating agent [3].…”

Section: Introductionmentioning

confidence: 99%

All-Trans Retinoic Acid Stimulates Viral Mimicry, Interferon Responses and Antigen Presentation in Breast-Cancer Cells

Bolis

Paroni

Fratelli

et al. 2020

Cancers

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All-trans retinoic acid (ATRA), a recognized differentiating agent, has significant potential in the personalized/stratified treatment of breast cancer. The present study reports on the molecular mechanisms underlying the anti-tumor activity of ATRA in breast cancer. The work is based on transcriptomic experiments performed on ATRA-treated breast cancer cell-lines, short-term tissue cultures of patient-derived mammary-tumors and a xenograft model. ATRA upregulates gene networks involved in interferon-responses, immune-modulation and antigen-presentation in retinoid-sensitive cells and tumors characterized by poor immunogenicity. ATRA-dependent upregulation of these gene networks is caused by a viral mimicry process, involving the activation of endogenous retroviruses. ATRA induces a non-canonical type of viral mimicry, which results in increased expression of the IRF1 (Interferon Responsive Factor 1) transcription factor and the DTX3L (Deltex-E3-Ubiquitin-Ligase-3L) downstream effector. Functional knockdown studies indicate that IRF1 and DTX3L are part of a negative feedback loop controlling ATRA-dependent growth inhibition of breast cancer cells. The study is of relevance from a clinical/therapeutic perspective. In fact, ATRA stimulates processes controlling the sensitivity to immuno-modulatory drugs, such as immune-checkpoint-inhibitors. This suggests that ATRA and immunotherapeutic agents represent rational combinations for the personalized treatment of breast cancer. Remarkably, ATRA-sensitivity seems to be relatively high in immune-cold mammary tumors, which are generally resistant to immunotherapy.

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Section: Introductionmentioning

confidence: 99%

All-Trans Retinoic Acid Stimulates Viral Mimicry, Interferon Responses and Antigen Presentation in Breast-Cancer Cells

Bolis

Paroni

Fratelli

et al. 2020

Cancers

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“…Peretinoin was found to activate transcription through retinoic acid receptor (RAR) and retinoid X receptor (RXR), and could activate the differentiation of human acute promyelocytic leukemia in HL-60 cells [ 22 , 23 ]. Peretinoin significantly inhibited hepatocarcinogenesis in rat chemical carcinogenesis models using 3′-methyl-4-(dimethylamino)azobenzene (3′-MeDAB) and diethylnitrosamine (DEN) [ 24 , 25 ], suggesting that peretinoin was also involved in suppressing hepatocarcinogenesis.…”

Section: Peretinoinmentioning

confidence: 99%

Peretinoin, an Acyclic Retinoid, for the Secondary Prevention of Hepatocellular Carcinoma

2021

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The high rates of hepatocellular carcinoma (HCC) recurrence after initially successful curative therapy emphasize ongoing unmet needs to prevent or reduce HCC recurrence. Retinoid acid (RA), a metabolite of vitamin A and its related analogues (termed retinoids) has been suggested as a promising chemotherapeutic agent in cancer treatment. The synthetic oral retinoid peretinoin is the only agent for the secondary chemoprevention of HCC after curative therapy that is currently well applied into clinical development. Here we present an updated summary of the molecular pathogenesis of HCC and of preclinical and clinical findings with peretinoin, including its clinical characteristics, safety and tolerability profile and future perspectives for clinical use.

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“…Retinoic acid, a bioactive metabolite of vitamin A, is involved in regulating a large number of biological processes including cellular proliferation, differentiation and apoptosis. RARs (RARα, RARβ and RARγ), and RXRs are the retinoid receptors [71,72]. Studies have shown that the aberrant expression of RARγ is associated with the development of cancers including hepatocellular carcinoma [73].…”

Section: Retinoic Acid Receptorsmentioning

confidence: 99%

Wnt/β-catenin signaling as an emerging potential key pharmacological target in cholangiocarcinoma

Qiu

Yang

et al. 2020

Bioscience Reports

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Cholangiocarcinoma (CCA) is a fatal malignant tumor of biliary epithelial cells involving intra- or extra-hepatic bile ducts. The prognosis of CCA is generally poor due to its diagnosis at the late stages. The currently employed chemotherapeutic agents do not increase the survival rate in patients with unresectable CCA. Accordingly, there is a need to identify new therapeutic agents for the effective management of intra- and extra-hepatic CCA. Clinical as well as preclinical studies have suggested the key role of the activation of Wnt/β-catenin signaling pathway in the induction and progression of CCA. There is an up-regulation of different Wnt ligands including Wnt2, Wnt3, Wnt5, Wnt7 and Wnt10 along with redistribution of β-catenin (more expression in the nucleus and lesser on the cell surface due to nuclear translocation of β-catenin) in different types of malignant biliary tumors. Apart from the role of this pathway in the induction and progression of CCA, this pathway is also involved in inducing multidrug resistance by inducing the expression of P-glycoprotein efflux pump on the cancer cells. These deleterious effects of Wnt/β-catenin signaling are mediated in association with other signaling pathways involving microRNAs (miRNAs), PI3K/AKT/PTEN/GSK-3β, retinoic acid receptors (RARs), dickkopf-1 (DKK1), protein kinase A regulatory subunit 1 α (PRKAR1A/PKAI), (SLAP), liver kinase B1 (LKB1) and CXCR4. The selective inhibitors of Wnt/β-catenin signaling may be potentially employed to overcome multidrug-resistant, fatal CCA. The present review discusses the role of Wnt/β-catenin along with its relation with other signaling pathways in the induction and progression of CCA.

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Retinoic Acid Receptors in Acute Myeloid Leukemia Therapy

Cited by 54 publications

References 113 publications

All-Trans Retinoic Acid Stimulates Viral Mimicry, Interferon Responses and Antigen Presentation in Breast-Cancer Cells

All-Trans Retinoic Acid Stimulates Viral Mimicry, Interferon Responses and Antigen Presentation in Breast-Cancer Cells

Peretinoin, an Acyclic Retinoid, for the Secondary Prevention of Hepatocellular Carcinoma

Wnt/β-catenin signaling as an emerging potential key pharmacological target in cholangiocarcinoma

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