Heterogeneity of triple-negative breast cancer: understanding the Daedalian labyrinth and how it could reveal new drug targets

Expert Opin Ther Targets. 2022 Jun;26(6):557-573. doi: 10.1080/14728222.2022.2084380. Epub 2022 Jun 8.

Abstract

Introduction: Triple-negative breast cancer (TNBC) is considered the most aggressive breast cancer subtype with the least favorable outcomes. However, recent research efforts have generated an enhanced knowledge of the biology of the disease and have provided a new, more comprehensive understanding of the multifaceted ecosystem that underpins TNBC.

Areas covered: In this review, the authors illustrate the principal biological characteristics of TNBC, the molecular driver alterations, targetable genes, and the biomarkers of immune engagement that have been identified across the subgroups of TNBC. Accordingly, the authors summarize the landscape of the innovative and investigative biomarker-driven therapeutic options in TNBC that emerge from the unique biological basis of the disease.

Expert opinion: The therapeutic setting of TNBC is rapidly evolving. An enriched understanding of the tumor spatial and temporal heterogeneity and the surrounding microenvironment of this complex disease can effectively support the development of novel and tailored opportunities of treatment.

Keywords: ADC; BRCAness; MAPK; PI3K-AKT-mTOR; TNBC subtypes; TROP-2; androgen receptor; epigenetics; immunotherapy; tumor heterogeneity.

Publication types

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

MeSH terms

  • Ecosystem
  • Humans
  • Triple Negative Breast Neoplasms* / drug therapy
  • Triple Negative Breast Neoplasms* / genetics
  • Triple Negative Breast Neoplasms* / pathology
  • Tumor Microenvironment