Deciphering and targeting oncogenic mutations and pathways in breast cancer

Libero Santarpia, Giulia Bottai, Catherine M. Kelly, B. Györffy, Borbala Székely, Lajos Pusztai

Research output: Contribution to journalReview article

24 Citations (Scopus)

Abstract

Advances in DNA and RNA sequencing revealed substantially greater genomic complexity in breast cancer than simple models of a fewdriver mutations would suggest. Only very few, recurrent mutations or copy-number variations in cancercausing genes have been identified. The two most common alterations in breast cancer are TP53 (affecting the majority of triple-negative breast cancers) and PIK3CA (affecting almost half of estrogen receptor-positive cancers) mutations, followed by a long tail of individually rare mutations affecting <1%–20% of cases. Each cancer harbors from a few dozen to a few hundred potentially high-functional impact somatic variants, along with a much larger number of potentially high-functional impact germline variants. It is likely that it isthe combined effect of all genomic variations that drives the clinical behavior of a given cancer. Furthermore, entirely new classes of oncogenic events are being discovered in the noncoding areas of the genome and in noncoding RNA species driven by errors in RNA editing. In light of this complexity, it is not unexpected that, with the exception of HER2 amplification, no robust molecular predictors of benefit from targeted therapies have been identified. In this review, we summarize the current genomic portrait of breast cancer, focusing on genetic aberrations that are actively being targeted with investigational drugs.

Original languageEnglish
Pages (from-to)1063-1078
Number of pages16
JournalOncologist
Volume21
Issue number9
DOIs
Publication statusPublished - Sep 1 2016

Fingerprint

Breast Neoplasms
Mutation
Triple Negative Breast Neoplasms
Investigational Drugs
RNA Editing
RNA Sequence Analysis
Neoplasms
Untranslated RNA
DNA Sequence Analysis
Estrogen Receptors
Genome
Genes
Therapeutics

Keywords

  • Biomarkers of response to therapy
  • Breast cancer molecular subtypes
  • Drug resistance
  • Mutation-genomic landscape
  • Oncogenic signaling pathways
  • Potential therapeutic targets
  • Tumor heterogeneity

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Santarpia, L., Bottai, G., Kelly, C. M., Györffy, B., Székely, B., & Pusztai, L. (2016). Deciphering and targeting oncogenic mutations and pathways in breast cancer. Oncologist, 21(9), 1063-1078. https://doi.org/10.1634/theoncologist.2015-0369

Deciphering and targeting oncogenic mutations and pathways in breast cancer. / Santarpia, Libero; Bottai, Giulia; Kelly, Catherine M.; Györffy, B.; Székely, Borbala; Pusztai, Lajos.

In: Oncologist, Vol. 21, No. 9, 01.09.2016, p. 1063-1078.

Research output: Contribution to journalReview article

Santarpia, L, Bottai, G, Kelly, CM, Györffy, B, Székely, B & Pusztai, L 2016, 'Deciphering and targeting oncogenic mutations and pathways in breast cancer', Oncologist, vol. 21, no. 9, pp. 1063-1078. https://doi.org/10.1634/theoncologist.2015-0369
Santarpia, Libero ; Bottai, Giulia ; Kelly, Catherine M. ; Györffy, B. ; Székely, Borbala ; Pusztai, Lajos. / Deciphering and targeting oncogenic mutations and pathways in breast cancer. In: Oncologist. 2016 ; Vol. 21, No. 9. pp. 1063-1078.
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