Small-molecule inhibitors of breast cancer-related targets: Potential therapeutic agents for breast cancer

Tingting Liu; Shubin Song; Xu Wang; Jifu Hao

doi:10.1016/j.ejmech.2020.112954

Small-molecule inhibitors of breast cancer-related targets: Potential therapeutic agents for breast cancer

Eur J Med Chem. 2021 Jan 15:210:112954. doi: 10.1016/j.ejmech.2020.112954. Epub 2020 Oct 29.

Authors

Tingting Liu¹, Shubin Song², Xu Wang³, Jifu Hao⁴

Affiliations

¹ Department of Medicinal Chemistry, School of Pharmacy, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, Shandong, 271016, PR China. Electronic address: liutingting@sdfmu.edu.cn.
² Department of Breast Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, PR China.
³ Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, United States.
⁴ Department of Medicinal Chemistry, School of Pharmacy, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, Shandong, 271016, PR China.

PMID: 33158576
DOI: 10.1016/j.ejmech.2020.112954

Abstract

Despite dramatic advances in cancer research and therapy, breast cancer remains a tricky health problem and represents a top biomedical research priority. Nowadays, breast cancer is still the leading cause of malignancy-related deaths in women, and incidence and mortality rates of it are expected to increase significantly the next years. Currently more and more researchers are interested in the study of breast cancer by its arising in young women. The common treatment options of breast cancer are chemotherapy, immunotherapy, hormone therapy, surgery, and radiotherapy. Most of them require chemical agents, such as PARP inhibitors, CDK4/6 inhibitors, and HER2 inhibitors. Recent studies suggest that some targets or pathways, including BRD4, PLK1, PD-L1, HDAC, and PI3K/AKT/mTOR, are tightly related to the occurrence and development of breast cancer. This article reviews the interplay between these targets and breast cancer and summarizes the progress of current research on small molecule inhibitors of these anti-breast cancer targets. The review aims to provide structural and theoretical basis for designing novel anti-breast cancer agents.

Keywords: Breast cancer; Inhibitor; Interplay; Therapy.

Publication types

Review

MeSH terms

Animals
Antineoplastic Agents / chemistry*
Antineoplastic Agents / pharmacology*
Antineoplastic Agents / therapeutic use
Breast Neoplasms / drug therapy*
Breast Neoplasms / metabolism
Cell Cycle Proteins / antagonists & inhibitors
Cell Cycle Proteins / metabolism
Drug Discovery
Female
Histone Deacetylase Inhibitors / chemistry
Histone Deacetylase Inhibitors / pharmacology
Histone Deacetylase Inhibitors / therapeutic use
Humans
Molecular Targeted Therapy
Phosphoinositide-3 Kinase Inhibitors / chemistry
Phosphoinositide-3 Kinase Inhibitors / pharmacology
Phosphoinositide-3 Kinase Inhibitors / therapeutic use
Polo-Like Kinase 1
Poly(ADP-ribose) Polymerase Inhibitors / chemistry
Poly(ADP-ribose) Polymerase Inhibitors / pharmacology
Poly(ADP-ribose) Polymerase Inhibitors / therapeutic use
Protein Serine-Threonine Kinases / antagonists & inhibitors
Protein Serine-Threonine Kinases / metabolism
Proto-Oncogene Proteins / antagonists & inhibitors
Proto-Oncogene Proteins / metabolism
Signal Transduction / drug effects*
Small Molecule Libraries / chemistry*
Small Molecule Libraries / pharmacology*
Small Molecule Libraries / therapeutic use
Transcription Factors / antagonists & inhibitors
Transcription Factors / metabolism

Substances

Antineoplastic Agents
BRD4 protein, human
Cell Cycle Proteins
Histone Deacetylase Inhibitors
Phosphoinositide-3 Kinase Inhibitors
Poly(ADP-ribose) Polymerase Inhibitors
Proto-Oncogene Proteins
Small Molecule Libraries
Transcription Factors
Protein Serine-Threonine Kinases