Sequential or Concomitant Inhibition of Cyclin-Dependent Kinase 4/6 Before mTOR Pathway in Hormone-Positive HER2 Negative Breast Cancer: Biological Insights and Clinical Implications

Giulia Occhipinti, Emanuela Romagnoli, Matteo Santoni, Alessia Cimadamore, Giulia Sorgentoni, Monia Cecati, Matteo Giulietti, Nicola Battelli, Alessandro Maccioni, Nadia Storti, Liang Cheng, Giovanni Principato, Rodolfo Montironi, Francesco Piva

Research output: Contribution to journalReview article

Abstract

About 75% of all breast cancers are hormone receptor-positive (HR+). However, the efficacy of endocrine therapy is limited due to the high rate of either pre-existing or acquired resistance. In this work we reconstructed the pathways around estrogen receptor (ER), mTOR, and cyclin D in order to compare the effects of CDK4/6 and PI3K/AKT/mTOR inhibitors. A positive feedback loop links mTOR and ER that support each other. We subsequently considered whether a combined or sequential inhibition of CDK4/6 and PI3K/AKT/mTOR could ensure better results. Studies indicate that inhibition of CDK4/6 activates mTOR as an escape mechanism to ensure cell proliferation. In literature, the little evidence dealing with this topic suggests that pre-treatment with mTOR pathway inhibitors could prevent or delay the onset of CDK4/6 inhibitor resistance. Additional studies are needed in order to find biomarkers that can identify patients who will develop this resistance and in whom the sensitivity to CDK4/6 inhibitors can be restored.

Original languageEnglish (US)
Article number349
JournalFrontiers in Genetics
Volume11
DOIs
StatePublished - Apr 15 2020

Keywords

  • CDK inhibitors
  • breast cancer
  • cyclin-dependent kinases (CDKs)
  • estrogen receptor
  • mechanisms of resistance

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Genetics(clinical)

Fingerprint Dive into the research topics of 'Sequential or Concomitant Inhibition of Cyclin-Dependent Kinase 4/6 Before mTOR Pathway in Hormone-Positive HER2 Negative Breast Cancer: Biological Insights and Clinical Implications'. Together they form a unique fingerprint.

  • Cite this

    Occhipinti, G., Romagnoli, E., Santoni, M., Cimadamore, A., Sorgentoni, G., Cecati, M., Giulietti, M., Battelli, N., Maccioni, A., Storti, N., Cheng, L., Principato, G., Montironi, R., & Piva, F. (2020). Sequential or Concomitant Inhibition of Cyclin-Dependent Kinase 4/6 Before mTOR Pathway in Hormone-Positive HER2 Negative Breast Cancer: Biological Insights and Clinical Implications. Frontiers in Genetics, 11, [349]. https://doi.org/10.3389/fgene.2020.00349