Research progress on the role of reactive oxygen species in the initiation, development and treatment of breast cancer.

Abstract

According to international cancer data, breast cancer (BC) is the leading type of cancer in women. Although significant progress has been made in treating BC, metastasis and drug resistance continue to be the primary causes of mortality for many patients. Reactive oxygen species (ROS) play a dual role in vivo: normal levels can maintain the body's normal physiological function; however, high levels of ROS below the toxicity threshold can lead to mtDNA damage, activation of proto-oncogenes, and inhibition of tumor suppressor genes, which are important causes of BC. Differences in the production and regulation of ROS in different BC subtypes have important implications for the development and treatment of BC. ROS can also serve as an important intracellular signal transduction factor by affecting the antioxidant system, activating MAPK and PI3K/AKT, and other signal pathways to regulate cell cycle and change the relationship between cells and the activity of metalloproteinases, which significantly impacts the metastasis of BC. Hypoxia in the BC microenvironment increases ROS production levels, thereby inducing the expression of hypoxia inducible factor-1α (HIF-1α) and forming "ROS- HIF-1α-ROS" cycle that exacerbates BC development. Many anti-BC therapies generate sufficient toxic ROS to promote cancer cell apoptosis, but because the basal level of ROS in BC cells exceeds that of normal cells, this leads to up-regulation of the antioxidant system, drug efflux, and apoptosis inhibition, rendering BC cells resistant to the drug. ROS crosstalks with tumor vessels and stromal cells in the microenvironment, increasing invasiveness and drug resistance in BC.

• Authors: Jing Zhong, Yan Tang
• Journal: Progress in biophysics and molecular biology (Prog Biophys Mol Biol) Vol. 188 Pg. 1-18 (May 2024) ISSN: 1873-1732 [Electronic] England
• PMID: 38387519 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2024 Elsevier Ltd. All rights reserved.

Chemical References

• Reactive Oxygen Species
• Antioxidants
• Phosphatidylinositol 3-Kinases

Topics

• Humans
• Female
• Reactive Oxygen Species (metabolism)
• Breast Neoplasms (drug therapy)
• Antioxidants
• Phosphatidylinositol 3-Kinases
• Hypoxia
• Tumor Microenvironment