RESUMO
Gastrointestinal (GI) malignancies account for substantial mortality and morbidity worldwide. They are generally promoted by dysregulated signal transduction and epigenetic pathways, which are controlled by specific enzymes. Recent studies demonstrated that histone deacetylases (HDACs) together with DNA methyltransferases (DNMTs) have crucial roles in the signal transduction/epigenetic pathways in GI regulation. In this review, we discuss various enzyme targets and their functional mechanisms responsible for the regulatory processes of GI malignancies. We also discuss the epigenetic therapeutic targets that are mainly facilitated by DNMT and HDAC inhibitors, which have functional consequences and clinical outcomes for GI malignancies.
Assuntos
Epigênese Genética , Neoplasias Gastrointestinais/tratamento farmacológico , Inibidores de Histona Desacetilases/farmacologia , Antineoplásicos/farmacologia , Metilases de Modificação do DNA/antagonistas & inibidores , Neoplasias Gastrointestinais/enzimologia , Neoplasias Gastrointestinais/genética , Histona Desacetilases/efeitos dos fármacos , Histona Desacetilases/metabolismo , Humanos , Terapia de Alvo MolecularRESUMO
Increases in Reactive oxygen species (ROS) have been reported in breast tumors and their surrounding tumor microenvironment (TME) cells. ROS are critical factors in breast TME as they ensure bidirectional communication among various components and mediate multi-faceted roles in tumor progression and metastasis. This paper presents a detailed and comprehensive review of the studies exploring ROS and various forms of oxidative stress in cancer progression, specifically breast cancer (BC), its microenvironment and associated cell types. The paper focuses on several diverse aspects of cellular and molecular biology of cancer, with pharmacological implications of phytochemicals in BC. We also describe the role of ROS in the genetic and epigenetic reprogramming of the TME, metastasis, and drug resistance as well as regulators of BC TME. Additionally, we discuss ROS-mediated TME therapy and the therapeutic conundrum of breast TME. These contributions could prompt the development of personalized anti-cancer drugs for the treatment of highly complex and aggressive BCs.