Moving Breast Cancer Therapy up a Notch

Erik W. J. Mollen, Jonathan Ient, Vivianne C. G. Tjan-Heijnen, Liesbeth J. Boersma, Lucio Miele, Marjolein L. Smidt, Marc A. G. G. Vooijs*

*Corresponding author for this work

Research output: Contribution to journal(Systematic) Review article peer-review

29 Citations (Web of Science)

Abstract

Breast cancer is the second most common malignancy, worldwide. Treatment decisions are based on tumor stage, histological subtype, and receptor expression and include combinations of surgery, radiotherapy, and systemic treatment. These, together with earlier diagnosis, have resulted in increased survival. However, initial treatment efficacy cannot be guaranteed upfront, and these treatments may come with (long-term) serious adverse effects, negatively affecting a patient's quality of life. Gene expression-based tests can accurately estimate the risk of recurrence in early stage breast cancers. Disease recurrence correlates with treatment resistance, creating a major need to resensitize tumors to treatment. Notch signaling is frequently deregulated in cancer and is involved in treatment resistance. Preclinical research has already identified many combinatory therapeutic options where Notch involvement enhances the effectiveness of radiotherapy, chemotherapy or targeted therapies for breast cancer. However, the benefit of targeting Notch has remained clinically inconclusive. In this review, we summarize the current knowledge on targeting the Notch pathway to enhance current treatments for breast cancer and to combat treatment resistance. Furthermore, we propose mechanisms to further exploit Notch-based therapeutics in the treatment of breast cancer.

Original languageEnglish
Article number518
Number of pages25
JournalFrontiers in Oncology
Volume8
DOIs
Publication statusPublished - 20 Nov 2018

Keywords

  • breast cancer
  • Notch
  • personalized precision treatment
  • treatment resistance
  • resensitisation
  • GAMMA-SECRETASE INHIBITORS
  • MAMMARY STEM-CELLS
  • ESTROGEN-RECEPTOR-ALPHA
  • COMPREHENSIVE MOLECULAR PORTRAITS
  • EPITHELIAL-MESENCHYMAL TRANSITION
  • ACUTE LYMPHOBLASTIC-LEUKEMIA
  • SIGNALING INDUCES APOPTOSIS
  • ADVANCED SOLID TUMORS
  • REGULATORY T-CELLS
  • CARCINOMA IN-SITU

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