Irreversible pan-ErbB tyrosine kinase inhibitors and breast cancer: Current status and future directions

2009 ◽  
Vol 35 (8) ◽  
pp. 685-691 ◽  
Author(s):  
Alberto Ocaña ◽  
Eitan Amir
Keyword(s):  
Breast Cancer ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Current Status ◽  
Future Directions

scholarly journals Anti-EGFR monoclonal antibodies and EGFR tyrosine kinase inhibitors as combination therapy for triple-negative breast cancer

Oncotarget ◽  
2016 ◽  
Vol 7 (45) ◽  
pp. 73618-73637 ◽  
Author(s):  
Abderrahim El Guerrab ◽  
Mahchid Bamdad ◽  
Fabrice Kwiatkowski ◽  
Yves-Jean Bignon ◽  
Frédérique Penault-Llorca ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Monoclonal Antibodies ◽  
Combination Therapy ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Triple Negative Breast Cancer ◽  
Kinase Inhibitors ◽  
Triple Negative ◽  
Egfr Tyrosine Kinase ◽  
Egfr Tyrosine Kinase Inhibitors

scholarly journals HER2-Targeted Tyrosine Kinase Inhibitors Cause Therapy-Induced-Senescence in Breast Cancer Cells

Cancers ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 197 ◽  
Author(s):  
Martina S.J. McDermott ◽  
Neil Conlon ◽  
Brigid C. Browne ◽  
Adam Szabo ◽  
Naoise C. Synnott ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tyrosine Kinase ◽  
Cancer Cells ◽  
Tyrosine Kinase Inhibitors ◽  
Cell Fate ◽  
Breast Cancer Cells ◽  
Kinase Inhibitors ◽  
Single Agent ◽  
Prolonged Treatment ◽  
Her2 Positive

Prolonged treatment of HER2 positive breast cancer cells with tyrosine kinase inhibitors (TKIs) leads to the emergence of acquired resistance. However, the effects of continuous TKI exposure on cell fate, and the steps leading to the acquisition of a resistant phenotype are poorly understood. To explore this, we exposed five HER2 positive cells lines to HER2 targeted therapies for periods of up to 4 weeks and examined senescence associated β-galactosidase (SA-β-gal) activity together with additional markers of senescence. We found that lapatinib treatment resulted in phenotypic alterations consistent with a senescent phenotype and strong SA-β-gal activity in HER2-positive cell lines. Lapatinib-induced senescence was associated with elevated levels of p15 and p27 but was not dependent on the expression of p16 or p21. Restoring wild type p53 activity either by transfection or by treatment with APR-246, a molecule which reactivates mutant p53, blocked lapatinib-induced senescence and caused increased cell death. In contrast to lapatinib, SA-β-gal activity was not induced by exposing the cells to trastuzumab as a single agent but co-administration of lapatinib and trastuzumab induced senescence, as did treatment of the cells with the irreversible HER2 TKIs neratinib and afatinib. Neratinib- and afatinib-induced senescence was not reversed by removing the drug whereas lapatinib-induced senescence was reversible. In summary, therapy-induced senescence represents a novel mechanism of action of HER2 targeting agents and may be a potential pathway for the emergence of resistance.

scholarly journals Significance of Tyrosine Kinase Inhibitors in the Treatment of Metastatic Breast Cancer

Breast Care ◽  
2009 ◽  
Vol 4 (6) ◽  
pp. 373-378 ◽  
Author(s):  
Christoph Mundhenke ◽  
Alexander Strauss ◽  
Christian Schem
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Metastatic Breast
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