Addition of all-trans-retinoic acid to omeprazole and sucralfate therapy improves the prognosis of gastric dysplasia

Abstract

Objective: To investigate the efficacy of all-trans retinoic acid (ATRA) in human gastric dysplasia. Methods: In this double-blind study, patients with precancerous gastric dysplasia with or without intestinal metaplasia (IM) received either conventional treatment consisting of omeprazole and sucralfate (control group) or conventional treatment plus ATRA. Gastric mucosal biopsies were performed before and after drug treatment and were analysed histologically; expression of retinoblastoma (Rb) protein and HER2 protein in gastric mucosa were measured using immunohistochemistry. Results: A total of 122 patients were included in the study, 63 in the ATRA group and 59 in the control group. In the ATRA group, dysplasia was attenuated in 43 out of 63 patients (68%) compared with 22 out of 59 patients (37%) in the control group; however, IM was not affected by treatment in either group. ATRA treatment was associated with significantly increased Rb expression and decreased HER2 expression in gastric mucosa. Conclusions: The use of conventional therapy plus ATRA for gastric dysplasia was associated with improved efficacy compared with conventional therapy alone. It was also accompanied by increased Rb expression and decreased HER2 expression in gastric mucosa. The addition of ATRA to conventional therapy for gastritis may improve the prognosis of gastric dysplasia.

Histone deacetylase inhibitor entinostat in combination with a retinoid downregulates HER2 and reduces the tumor initiating cell population in aromatase inhibitor-resistant breast cancer

“…We have demonstrated that treatment with ENT reduces HER2 expression via degradation of chaperone protein hsp90 [8]. ATRA has also been shown to downregulate HER2; Jin et al showed that treatment with ATRA reduced HER2 expression in gastric dysplasia [17]. This data supports findings from Grunt and colleagues who observed downregulation of HER2 in breast cancer cell lines SkBR3 and BT474 following treatment with ATRA; this downregulation was postulated to be through inhibition of the transcription factor AP-1 [18].…”

Pin1 inhibition potently suppresses gastric cancer growth and blocks PI3K/AKT and Wnt/β‐catenin oncogenic pathways

“…ATRA, a therapy that has transformed the treatment of APL, has been shown to inhibit gastric cancer in cancer cell models and even in human patients, with anticancer mechanisms being traditionally attributed to activation of retinoic acid receptor (RARs) or retinoid X receptor (RXRs) . However, our recent mechanism‐based drug screens have surprisingly identified that ATRA is a Pin1 inhibitor.…”

“…Although a small study of 182 cases has shown Pin1 overexpression in human gastric cancer, the role of Pin1 in the development and treatment of gastric cancer is still unknown. Moreover, although ATRA has been shown to inhibit gastric cancer in cancer cell models and even in human patients, it is not known whether Pin1 plays any role in mediating its anticancer activity in gastric cancer.…”

Efficiency of All-Trans Retinoic Acid on Gastric Cancer: A Narrative Literature Review

“…In 2015, Jin J et al showed that patients with gastric dysplasia treated with omeprazole and sucralfate, associated to ATRA, presented a better attenuation of their dysplasia (68% vs. 37%) compared to patient treated with omeprazole and sucralfate alone. This was accompanied with an increased expression of the tumor suppressor pRb and a decreased expression of HER2 oncogenic receptor in patient’s gastric mucosa [ 99 ].…”