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Front. Oncol. | doi: 10.3389/fonc.2018.00518

Moving breast cancer therapy up a Notch

 Erik Mollen1, 2, Vivianne Tjan-Heijnen1, Liesbeth Boersma3,  Lucio Miele4, Marjolein Smidt1 and  Marc Vooijs1, 2, 3*
  • 1Maastricht University Medical Centre, Netherlands
  • 2Maastricht University, Netherlands
  • 3Maastro Clinic, Netherlands
  • 4School of Medicine, Louisiana State University, United States

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 – and potentially other malignancies.

Keywords: breast cancer, Notch, Personalized precision treatments, treatment resistance, Resensitization

Received: 18 Jul 2018; Accepted: 22 Oct 2018.

Edited by:

Giorgio Seano, Institut Curie, France

Reviewed by:

Gino B. Ferraro, Harvard Medical School, United States
Isabella Screpanti, La Sapienza University of Rome, Italy  

Copyright: © 2018 Mollen, Tjan-Heijnen, Boersma, Miele, Smidt and Vooijs. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Marc Vooijs, Maastro Clinic, Maastricht, Netherlands,