New Advances in Targeted Therapy of HER2-Negative Breast Cancer

Abstract

Breast cancer has an extremely high incidence in women, and its morbidity and mortality rank first among female tumors. With the increasing development of molecular biology and genomics, molecular targeted therapy has become one of the most active areas in breast cancer treatment research and has also achieved remarkable achievements. However, molecular targeted therapy is mainly aimed at HER2-positive breast cancer and has not yet achieved satisfactory curative effect on HER2-negative breast cancer. This article describes the potential targets that may be used for breast cancer treatment from the aspects of PI3K/AKT signaling pathway, DDR, angiogenesis, the cell cycle, breast cancer stem cells, etc., and explores possible inhibitors for the treatment of HER2-negative breast cancer, such as PI3K inhibitors, AKT inhibitors and m-TOR inhibitors that inhibit the PI3K/AKT signaling pathway, small molecule tyrosine kinase inhibitors that restrain angiogenesis, CDK inhibitors, aurora kinase inhibitors and HDAC inhibitors that block cell cycle, as well as the drugs targeting breast cancer stem cells which have been a hit, aiming to provide a new idea and strategy for the treatment of HER2-negative breast cancer.

Anticancer Studies of Newly Synthesized Thiazole Derivatives: Synthesis, Characterization, Biological Activity, and Molecular Docking

“…In addition, the protons of the azomethine (CH=N) and methylene group in the thiazole ring appeared at δ 8.24 and 3.91 ppm as singlet signals, while the protons of the aromatic group were observed at δ 7.24 and 7.81 ppm as doublet signals; the 13 CNMR spectrum of compound 5 displayed new two carbon signals at δ169.50 and 25.35 ppm due to the acetyloxy group (OCOCH 3 ). Furthermore, treatment of the thiazole derivative (4a) with 3-methoxy-4-hydroxybenzaldehyde in dimethyl formamide in the presence of fused sodium acetate under reflux produced 5-(4-hydroxy-3methoxybenzylidene)-2-(2-4-hydroxybenzylidene)hydrazinyl)thiazole-4[5H]-one (6). The structure of the compounds was validated by spectral data ( 1 HNMR, 13 CNMR) (in Supplementary Materials).…”

“…Additionally, various conservative therapies are dependent on synthetic anticancer drugs, including chemotherapy and targeted therapies. Consequently, researchers focus their interests on discovering and developing novel, safe, and effective compounds for cancer therapy with minimum side effects [5,6].…”

Oxygen tension-dependent variability in the cancer cell kinome impacts signaling pathways and response to targeted therapies

“… 3 , 4 In breast cancer, targeted therapies are being developed and/or used toward multiple oncogenic signaling pathways involving receptor tyrosine kinases (RTKs) such as the epidermal growth factor receptor (EGFR) and protein kinases such as protein kinase B (PKB/AKT) and extracellular regulated kinase (ERK). 5 In many cancers, resistance to targeted therapies is mediated via various mechanisms that allow cancer cells to bypass targeted pathways, alter drug targets by activating downstream effectors, or adopt phenotypic changes that contribute to drug resistance. 6 Notably, the crosstalk between the RAF-MEK-ERK and phosphatidylinositol 3-kinase (PI3K)/AKT signaling axis has been demonstrated to contribute to resistance to therapies targeting either pathway.…”

Novel 1,3-Thiazole Analogues with Potent Activity against Breast Cancer: A Design, Synthesis, In Vitro, and In Silico Study

“…Further, side effects might include osteoporosis, cardiovascular problems, and induced drug resistance. Accordingly, there is an urgent demand for continuous progress in the discovery and development of novel, safe, and effective lead compounds for long-term cancer therapy with less side effects [ 6 , 7 , 8 , 9 ].…”