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. 2020 Jun 10;21(11):4154.
doi: 10.3390/ijms21114154.

Ibrutinib in Gynecological Malignancies and Breast Cancer: A Systematic Review

Julian Matthias Metzler  1 , Laurin Burla  1 , Daniel Fink  1 , Patrick Imesch  1
Affiliations

Ibrutinib in Gynecological Malignancies and Breast Cancer: A Systematic Review

Julian Matthias Metzler et al. Int J Mol Sci. .

Abstract

Ibrutinib is an orally available, small-molecule tyrosine kinase inhibitor. Its main purpose is to inhibit Bruton's tyrosine kinase (BTK), an enzyme that is crucial in B cell development. It is FDA approved for the treatment of certain hematological malignancies. Several promising off-target drug effects have led to multiple, mostly preclinical investigations regarding its use in solid tumors. Unfortunately, data on its effectiveness in gynecological malignancies are limited, and (systematic) reviews are missing. The objective of this review was to summarize the existing literature and to analyze the evidence of ibrutinib as a treatment option in gynecological malignancies, including breast cancer. Studies were identified in MEDLINE and EMBASE using a defined search strategy, and preclinical or clinical research projects investigating ibrutinib in connection with these malignancies were considered eligible for inclusion. Our findings showed that preclinical studies generally confirm ibrutinib's efficacy in cell lines and animal models of ovarian, breast, and endometrial cancer. Ibrutinib exerts multiple antineoplastic effects, such as on-target BTK inhibition, off-target kinase inhibition, and immunomodulation by interference with myeloid-derived suppressor cells (MDSCs), programmed death-ligand 1 (PD-L1), and T cell response. These mechanisms were elaborated and discussed in the context of the evidence available. Further research is needed in order to transfer the preclinical results to a broader clinical appliance.

Keywords: Bruton’s tyrosine kinase; Btk; breast cancer; endometrial cancer; gynecologic oncology; gynecology; ibrutinib; kinase inhibitor; ovarian cancer; solid tumors.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure A1
Figure A1
Search results of clinical trials.
Figure 1
Figure 1
Flow diagram for the identification of relevant studies.
See this image and copyright information in PMC

References

    1. Dubovsky J.A., Beckwith K.A., Natarajan G., Woyach J.A., Jaglowski S., Zhong Y., Hessler J.D., Liu T.-M., Chang B.Y., Larkin K.M., et al. Ibrutinib is an irreversible molecular inhibitor of ITK driving a Th1-selective pressure in T lymphocytes. Blood. 2013;122:2539–2549. doi: 10.1182/blood-2013-06-507947. - DOI - PMC - PubMed
    1. Chen J., Kinoshita T., Sukbuntherng J., Chang B.Y., Elias L. Ibrutinib Inhibits ERBB Receptor Tyrosine Kinases and HER2-Amplified Breast Cancer Cell Growth. Mol. Cancer Ther. 2016;15:2835–2844. doi: 10.1158/1535-7163.MCT-15-0923. - DOI - PubMed
    1. Campbell R., Chong G., Hawkes E. Novel Indications for Bruton’s Tyrosine Kinase Inhibitors, beyond Hematological Malignancies. J. Clin. Med. 2018;7:62. doi: 10.3390/jcm7040062. - DOI - PMC - PubMed
    1. Molina-Cerrillo J., Alonso-Gordoa T., Gajate P., Grande E. Bruton’s tyrosine kinase (BTK) as a promising target in solid tumors. Cancer Treat. Rev. 2017;58:41–50. doi: 10.1016/j.ctrv.2017.06.001. - DOI - PubMed
    1. Pharmacyclics Inc. Imbruvica® (ibrutinib) [package insert]. U.S. Food and Drug Administration Website. [(accessed on 1 January 2020)]; Available online: www.accessdata.fda.gov/drugsatfda_docs/label/2019/205552s029,210563s004l....

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