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Published on: March 6, 2018
Exploring the logic and conducting a comprehensive evaluation of AdipoRon-based adiponectin replacement therapy
Lucas Fornari Laurindo1,2, Andreline Franchi Sosin3, Caroline Barbalho Lamas4
1Department of Biochemistry and Pharmacology, School of Medicine, Faculdade de Medicina de Marília (FAMEMA), Marília, São Paulo, 17519-030, Brazil. lucasffffor@gmail.com.
Abstract:
The potential benefits of adiponectin replacement therapy extend to numerous human diseases, with current research showing particular interest in its effectiveness against specific cancer forms, especially hormone-related. However, limitations in the pharmacological use of the intact protein have led to a focus on alternative options. AdipoRon is an extensively studied non-peptidic drug candidate for adiponectin replacement therapy. While researchers have explored the efficacy and therapeutic applications of AdipoRon in various disease conditions, their effects against cancer models advanced more, with no review regarding AdipoRon's efficacy against hormone-related cancers being published. The present systematic review aims to fill this gap. Preclinical evidence was compiled from PubMed, EMBASE, COCHRANE, and Google Scholar following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and the manuscript's quality assessment was conducted using the Joanna Briggs Institute (JBI) Checklist Critical Appraisal Tool for Systematic Reviews' Quality. The included nine studies incorporated various cell and animal models of the pancreas, gynaecological system, and osteosarcoma cancers. AdipoRon demonstrated effectiveness against pancreatic cancer by activating p44/42 MAPK, mitochondrial dysfunction, and AMPK-mediated inhibition of ACC1. In gynaecological cancers, it exhibited promising anticancer effects through the activation of AMPK, potential inhibition of mTOR, and modulation of the SET1B/BOD1/AdipoR1 signaling cascade. Against osteosarcoma, AdipoRon worked by perturbing ERK1/2 signaling and reducing p70S6K phosphorylation. AdipoRon shows promise in preclinical studies, but human trials are crucial for clinical safety and effectiveness. Caution is needed due to potential off-target effects, especially in cancer therapy with multi-target approaches. Structural biology and computational methods can help predict these effects.
Insights
AdipoRon, a non-peptidic drug, shows promise in preclinical studies for treating pancreatic, gynecological, and osteosarcoma cancers by targeting specific molecular pathways. Further human trials are essential to confirm its safety and effectiveness in cancer therapy.
Area of Science:
- Oncology
- Pharmacology
- Biochemistry
Background:
- Adiponectin replacement therapy offers potential benefits for various diseases, including hormone-related cancers.
- Limitations of using intact adiponectin protein have shifted focus to alternative drug candidates like AdipoRon.
- No systematic review specifically addresses AdipoRon's efficacy against hormone-related cancers.
Conclusions:
- AdipoRon exhibits significant preclinical anticancer potential across diverse cancer types.
- Further human clinical trials are imperative to establish AdipoRon's safety and efficacy.
- Potential off-target effects warrant careful consideration, especially with multi-target therapeutic strategies.
