The Multi-Omic Landscape of Primary Breast Tumors and Their Metastases: Expanding the Efficacy of Actionable Therapeutic Targets

Genes (Basel). 2022 Aug 29;13(9):1555. doi: 10.3390/genes13091555.

Abstract

Breast cancer (BC) mortality is almost exclusively due to metastasis, which is the least understood aspect of cancer biology and represents a significant clinical challenge. Although we have witnessed tremendous advancements in the treatment for metastatic breast cancer (mBC), treatment resistance inevitably occurs in most patients. Recently, efforts in characterizing mBC revealed distinctive genomic, epigenomic and transcriptomic (multi-omic) landscapes to that of the primary tumor. Understanding of the molecular underpinnings of mBC is key to understanding resistance to therapy and the development of novel treatment options. This review summarizes the differential molecular landscapes of BC and mBC, provides insights into the genomic heterogeneity of mBC and highlights the therapeutically relevant, multi-omic features that may serve as novel therapeutic targets for mBC patients.

Keywords: DNA methylation alterations; genomic landscape; metastatic breast cancer; tumor microenvironment.

Publication types

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

MeSH terms

  • Biomarkers, Tumor* / genetics
  • Breast / pathology
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / pathology
  • Female
  • Genomics / methods
  • Humans

Substances

  • Biomarkers, Tumor

Grants and funding

The G.L. laboratory is supported in part by the generous contribution of George and Vicky Joseph. G.L. and DJW are supported by the National Cancer Institute (P30 CA014089).