Insights into breast cancer phenotying through molecular omics approaches and therapy response.

Jose E Belizario,Angela F Loggulo

doi:10.20517/cdr.2018.009

Abstract

Breast cancer is the most common cancer in the world. Despite advances in early detection and understanding of the molecular bases of breast cancer biology, approximately 30% of all patients with early-stage breast cancer have metastatic disease. Breast cancers are comprised of molecularly distinct subtypes that respond differently to pathway-targeted therapies and neoadjuvant systemic therapy. However, no tumor response is observed in some cases and development of resistance is most commonly seen in patients with heterogeneous breast cancer subtype. To offer better treatment with increased efficacy and low toxicity of selecting therapies, new technologies that incorporate clinical and molecular characteristics of intratumoral heterogeneity have been investigated. This short review provides some examples of integrative omics approaches (genome, epigenome, transcriptome, immune profiling) and mathematical/computational analyses that provide mechanistic and clinically relevant insights into underlying differences in breast cancer subtypes and patients’responses to specific therapies.

Highlights

Cancer is defined as genetic disease and is molecularly characterized by accumulation of mutations and epimutations that lead to functional dysregulation of cell genome and epigenome-driven processes[1].www.cdrjournal.comBelizario et al
What substantially contribute to oncogenesis and progression of tumors is intra and inter-clonal heterogeneity, which is determined by a stochastic mutational process in cancer cells[9,10]
A study in a Brazilian cohort of breast cancer patients confirmed that cancerassociated fibroblasts (CAFs) in lymph nodes with macrometastasis express similar profile of vimentin, alpha-smooth muscle actin (-SMA), and S100A4 protein as those CAFs found in primary tumors

Summary

Introduction

Cancer is defined as genetic disease and is molecularly characterized by accumulation of mutations and epimutations that lead to functional dysregulation of cell genome and epigenome-driven processes[1].www.cdrjournal.comBelizario et al. The functional consequence of most cancer mutations could be characterized in phenotypic readouts such as growth assays or drug response screens using tumor cell lines[5,6,7]. TNBCs display stem cell-like and luminal progenitor-like gene signatures, and frequently have somatic mutations in the TSGs TP53 and PTEN, and a smaller fraction is mutant for breast cancer 1 (BRCA1).

Results

Conclusion