Background: Tamoxifen is widely administered for patients with estrogen receptor-positive
breast cancer. Despite many patients benefiting from Tamoxifen as an effective anti-hormonal agent in
adjuvant therapy, a noticeable number of patients tend to develop resistance.
Objective: The aim of this study was to shed light upon the molecular mechanisms associated with Tamoxifen
resistance which can help improve current treatment strategies available for stimulating responsiveness
and combating resistance.
Methods: Relevant articles were obtained from PubMed and google scholar, nearly all dated from 2010
to 2017. Articles were screened to select the ones meeting the objective. The molecular interactions in
the resistant network were extracted from the appropriate articles.
Results: The mechanisms of developing Tamoxifen resistance were briefly outlined. Overactivation of
Receptor Tyrosine Kinases (RTKs) pathways, commonly known as alternative growth cascades, is one
of the main players in acquired cancer cell stemness, which can induce unrestricted proliferation in the
presence of Tamoxifen. There are seven recent patents including 6291496B1 as an anti-HER2,
8143226B2 as an inhibitor of RTK phosphorylation, 9062308B2 as an anti-HOXB7, Lapatinib functioning
as an anti-EGFR/HER2, Everolimus as an inhibitor of mTOR, Exemestane as an aromatase inhibitor
and Perifosine as an AKT inhibitor.
Conclusion: Altogether, it seems that tumor cells express a stemness phenotype which tends to override
anti-hormonal adjuvant therapies. Since RTKs are overactivated and overexpressed in such cells, specialized
targeted therapies suppressing RTKs would be a novel and effective way in restoring Tamoxifen
sensitivity in resistant breast cancer tumor cells.