Novel combinatorial strategies for boosting the efficacy of immune checkpoint inhibitors in advanced breast cancers

• M. F. Tolba ^[1] ; H. Elghazaly ^[4] ; E. Bousoik ^[5] ; M. M. A. Elmazar ^[2] ; S. M. Tolaney ^[3]
  1. [1] Ain Shams University

     Ain Shams University

     Egipto

     
  2. [2] British University in Egypt

     British University in Egypt

     Egipto

     
  3. [3] Harvard Medical School

     Harvard Medical School

     City of Boston, Estados Unidos

     
  4. [4] School of Life and Medical Sciences, University of Hertfordshire-Hosted By Global Academic Foundation, New Capital City, Egypt
  5. [5] Department of Biomedical and Pharmaceutical Sciences, Chapman University School of Pharmacy, Chapman University, Irvine, CA, USA

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• Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 23, Nº. 10, 2021, págs. 1979-1994
• Idioma: inglés
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• Resumen

  • The year 2019 witnessed the first approval of an immune checkpoint inhibitor (ICI) for the management of triple negative breast cancers (TNBC) that are metastatic and programmed death ligand (PD)-L1 positive. Extensive research has focused on testing ICI-based combinatorial strategies, with the ultimate goal of enhancing the response of breast tumors to immu- notherapy to increase the number of breast cancer patients benefiting from this transformative treatment. The promising investigational strategies included immunotherapy combinations with monoclonal antibodies (mAbs) against human epi- dermal growth factor receptor (HER)-2 for the HER2 + tumors versus cyclin-dependent kinase (CDK)4/6 inhibitors in the estrogen receptor (ER) + disease. Multiple approaches are showing signals of success in advanced TNBC include employing Poly (ADP-ribose) polymerase (PARP) inhibitors, tyrosine kinase inhibitors, MEK inhibitors, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling inhibitors or inhibitors of adenosine receptor, in combination with the classical PD-1/PD-L1 immune checkpoint inhibitors. Co-treatment with chemotherapy, high intensity focused ultrasound (HIFU) or interleukin-2-βɣ agonist have also produced promising outcomes. This review highlights the latest combinatorial strategies under development for overcoming cancer immune evasion and enhancing the percentage of immunotherapy responders in the different subsets of advanced breast cancers.