Dados do Resumo

Título

Exploring the rationale and conducting a comprehensive evaluation of AdipoRon-based adiponectin replacement therapy against hormone-related cancer - a systematic review

Introdução

Adiponectin is an attractive protein due to its therapeutic potential in several diseases. However, its pharmacological use still faces challenges, such as difficulty in administration and the need for high dosages. This led to the development of alternatives such as AdipoRon, a non-peptide drug that is a selective adiponectin receptor agonist with the potential to replace adiponectin in several therapeutic occasions, being studied in the treatment of hormonal cancers.

Objetivo

Given the scenario presented above, in which the efficiency of the AdipoRon protein has not yet been comprehensively reviewed, this systematic study aims to evaluate the efficacy of AdipoRon as an adiponectin replacement therapy, with a specific focus on hormonal cancers.

Métodos

The review was conducted following the PRISMA guidelines, with data collection from databases such as PubMed, EMBASE and COCHRANE and researchers such as Google Scholar. The quality assessment of the studies was carried out using the Joanna Briggs Institute (JBI) Critical Appraisal tool. Nine studies that used cellular and animal models for pancreatic, gynecological and osteosarcoma cancers were included.

Resultados

Studies have shown that AdipoRon has notable anti-cancer effects on different types of cancer. In pancreatic cancer, AdipoRon activated the p44/42 MAPK pathway, leading to mitochondrial dysfunction that impairs energy production in tumor cells, and inhibited the ACC1 enzyme, crucial for lipid biosynthesis, which can support tumor growth. In gynecological cancers, AdipoRon activated AMPK, a key protein for cellular energy metabolism, which can lead to inhibition of the mTOR pathway, involved in cell growth. Furthermore, AdipoRon modulated the SET1B/BOD1/AdipoR1 cascade, indicating further regulation of cell proliferation. Against osteosarcoma, AdipoRon disrupted ERK1/2 signaling, which is vital for tumor cell survival, and reduced the phosphorylation of p70S6K, an important factor in protein synthesis.

Conclusões

In light of the above, it is clear that AdipoRon demonstrates significant anticancer potential in preclinical studies. However, clinical trials are needed to confirm its safety and effectiveness in humans. Caution should be exercised due to possible off-target effects, especially in multi-target therapies. Structural and computational biology methods can be useful in predicting these effects.

Palavras Chave

AdipoRon; Adiponectin; Câncer