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MADRID, April 11 (EUROPA PRESS) –
Spanish researchers from the network of the Center for Biomedical Research for Cancer (CIBERONC) have discovered a new vulnerability of HER2 + breast cancer tumor cells, which offers a therapeutic opportunity to fight against trastuzumab resistance.
In recent years, and thanks to the development of new targeted therapies, the prognosis and life expectancy of patients with HER2 positive subtype breast cancer has improved significantly. However, in the advanced stages, it is common to find patients in whom tumors progress because of resistance to available treatments.
Trastuzumab is an antibody to HER2 that is used to treat patients with HER2-positive tumors. After generating experimental models of trastuzumab resistance, it was found that these resistant cells showed deregulation of the death pathways and specifically TRAIL-induced cell death.
This deregulation is due to an increase in cellular receptors of this factor, along with decreasing the amount of other inhibitory proteins in the system. As with FLIP. This combination makes the formation of the active functional complex (death-inducing complex, DISC) more efficient by promoting greater sensitivity to TRAIL of trastuzumab-resistant cells. Moreover, by means of gain or loss of function experiments, the importance of the different proteins involved in the activation of this pathway has been confirmed.
Finally, analysis of samples from patients with HER2 positive breast cancer validated the deregulation of this signaling pathway in patients resistant to trastuzumab. The importance of this study, led by Atanasio Pandiella of the Salamanca Cancer Research Center and Joaquín Arribas of the Institute of Oncology of Vall de Hebron in Barcelona, is that a vulnerability has been identified in the cells resistant to cancer. anticancer treatments. HER2, which could be exploited therapeutically.
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