Retinoids in cancer chemoprevention and therapy: Meta-analysis of randomized controlled trials

Abstract

Retinoids, natural and synthetic derivatives of vitamin A, have many regulatory functions in human body, including regulating cellular proliferation, differentiation, apoptosis. Moreover, retinoids have been used successfully for the treatment of certain malignancies, especially acute promyelocytic leukemia (APL) in adults and neuroblastoma in children. However, retinoids have not yet been translated into effective systemic treatments for most solid cancers. Some recent studies have shown that retinoids promote tumorigenesis. Therefore, we performed this meta-analysis to systematically evaluate the efficacy of retinoids in the chemoprevention and treatment of cancers. We performed literature search of several electronic databases, including PubMed, Embase and Cochrane Library from 2000 January to 2021 November. Various outcomes were applied to investigate the potential of retinoids for prevention and treatment of cancers. The primary outcomes in this study were disease recurrence and clinical response. The secondary outcomes included overall survival (OS), cancer development, disease progression and event-free survival. We identified 39 randomized controlled trials with 15,627 patients in this study. Our results showed that lower recurrence rate and better clinical response were obtained in retinoids treated patients with cancer or premalignancy as compared with control. The differences were statistically significant (RR = 0.85, 95% CI = 0.74–0.96, p = 0.01; RR = 1.24, 95% CI = 1.03–1.49, p = 0.02, respectively). Retinoids treatment was not associated with improvement in overall survival, cancer development, disease progression or event-free survival. Subgroup analysis conducted based on cancer type showed that patients benefited from retinoids treatment in APL, renal cell carcinoma, hepatocellular carcinoma, lung cancer, Kaposi sarcoma, and complete hydatidiform mole. No significant therapeutic effect was noted in head and neck cancer, acute myeloid leukemia (AML), melanoma, breast cancer, bladder cancer, cervical intraepithelial neoplasia (CIN) or cervical carcinoma. Subgroup analysis based on tumor classification demonstrated that retinoids group obtained a lower recurrence rate and better clinical response than control group in solid cancers. In conclusion, clinical application of retinoids was associated with reduction in disease recurrence and improvement in clinical response, illustrating that retinoids play a key role in cancer prevention and therapy. Further research is needed to broaden the utility of retinoids in other types of cancers.Systematic Review Registration: PROSPERO, identifier CRD42022296706.

Racial Disparities in the Genetic Landscape of Acute Myeloid Leukaemia from The Cancer Genome Atlas: Insights from a Bioinformatics Analysis

“…Despite a mixed outcome across leukaemia subtypes, retinoic acid treatment has shown promise as a cancer therapy, with emerging biomarkers suggesting that certain subgroups may exhibit enhanced sensitivity [74]. Combination therapy, including retinoids is therefore a promising approach [75].…”

Vitamin A: too good to be bad?

“…Different organizations and countries recommend minimum and maximum values for VA intake for children, adults, men, and normal women, pregnant and lactating women. Based on the important functions of VA and diseases that are directly or indirectly connected with VA signaling pathways, this vitamin is intensively discussed as a therapeutic compound to cure various diseases ( Chen et al, 2022 ; Cook et al, 2022 ; Sajovic et al, 2022 ; Zawada et al, 2023 ). In liver disease, for example, a low circulating retinol level was associated with liver fibrosis and liver-related mortality in chronic liver disease, suggesting that supplementation with VA might have direct therapeutic implications ( Song and Jiang, 2023 ).…”

ERβ1 Sensitizes and ERβ2 Desensitizes ERα-Positive Breast Cancer Cells to the Inhibitory Effects of Tamoxifen, Fulvestrant and Their Combination with All-Trans Retinoic Acid

“…Retinoids, such as all-trans retinoic acid (ATRA, the major active form of vitamin A), inhibit proliferation and viability of tamoxifen-sensitive and tamoxifen-resistant ERα-positive BC cells and the growth of experimental ERα-positive breast tumors, but they reportedly have no effect on the survival of breast cancer patients whether administered alone or in combination with tamoxifen [ 4 , 5 ]. The anticancer activity of retinoids is mediated by three retinoic acid receptor isotypes (RARα, RARβ and RARγ) and three retinoid X receptor isotypes (RXRα, RXRβ and RXRγ) [ 6 ].…”