Triple-negative breast cancer therapeutic resistance: Where is the Achilles' heel?

Xupeng Bai; Jie Ni; Julia Beretov; Peter Graham; Yong Li

doi:10.1016/j.canlet.2020.10.016

Triple-negative breast cancer therapeutic resistance: Where is the Achilles' heel?

Cancer Lett. 2021 Jan 28:497:100-111. doi: 10.1016/j.canlet.2020.10.016. Epub 2020 Oct 16.

Authors

Xupeng Bai¹, Jie Ni¹, Julia Beretov², Peter Graham¹, Yong Li³

Affiliations

¹ St George and Sutherland Clinical School, Faculty of Medicine, UNSW Sydney, Kensington, NSW, 2052, Australia; Cancer Care Centre, St. George Hospital, Kogarah, NSW, 2217, Australia.
² St George and Sutherland Clinical School, Faculty of Medicine, UNSW Sydney, Kensington, NSW, 2052, Australia; Cancer Care Centre, St. George Hospital, Kogarah, NSW, 2217, Australia; Anatomical Pathology, NSW Health Pathology, St. George Hospital, Kogarah, NSW, 2217, Australia.
³ St George and Sutherland Clinical School, Faculty of Medicine, UNSW Sydney, Kensington, NSW, 2052, Australia; Cancer Care Centre, St. George Hospital, Kogarah, NSW, 2217, Australia; School of Basic Medical Sciences, Zhengzhou University, Henan, 450001, China. Electronic address: y.li@unsw.edu.au.

PMID: 33069769
DOI: 10.1016/j.canlet.2020.10.016

Abstract

Triple-negative breast cancer (TNBC) shows a higher response rate to systemic therapy compared with other breast cancer subtypes. However, the tumor differentiation of TNBC is poorer, with an early tendency to metastasis and a higher recurrence rate. Relapsed and metastatic TNBCs usually progress more rapidly, showing strong resistance to chemotherapy and radiotherapy. Due to the lack of combinatorial targeted drugs, alternative treatments fail to improve these patient's prognosis and the quality of life. Finding the Achilles' heel of TNBC is critical for patients with advanced TNBC. Here, we summarize the latest advances in the mechanisms underlying TNBC therapeutic resistance, consider how these mechanisms may affect the development and utilization of TNBC targeted drugs, and discuss the rationale of relevant signals as therapeutic targets. Also, we review the clinical trials registered in ClinicalTrial.gov for TNBC patients, which comprehensively reveals current research and development of novel TNBC targeted drugs and future trends.

Keywords: Clinical trial; DNA repair; Immunotherapy; TNBC; Targeted drug; Therapeutic resistance; Tumor microenvironment.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Antineoplastic Agents / therapeutic use*
Drug Resistance, Neoplasm*
Female
Humans
Molecular Targeted Therapy*
Triple Negative Breast Neoplasms / drug therapy*
Triple Negative Breast Neoplasms / metabolism
Triple Negative Breast Neoplasms / pathology

Substances

Antineoplastic Agents