Overcome resistance
Currently, the drug neratinib, which is an inhibitor of the HER2 receptor, is undergoing clinical trials. The promising drug shows good efficacy in patients with cancer associated with a mutation of the HER2 gene (HER2-positive cancer). However, after a high first response to therapy, patients further develop resistance to the drug.
Scientists from the Harold Simmons Southwest Cancer Center at the University of Texas at Dallas found that another drug already on sale counteracts this resistance. We are talking about everolimus, a TORC1 inhibitor approved for the treatment of other types of breast cancer.
This discovery may provide clinicians with an effective way to overcome resistance to neratinib and successfully treat patients with breast, ovarian, lung and other cancers associated with the mutation of the HER2 gene.
The authors of this study focused on the signaling pathway controlled by the TORC1 protein, through which, as they showed, HER2-mutant cancer becomes resistant to neratinib. They noticed activation of TORC1 signaling during the development of resistance to neratinib.
Source: article in Cancer Cell.
DNA sequencing of cancer cells in patients before and during the clinical trial with neratinib showed that some patients already had a mutation that could activate the TORC1 pathway; in other patients, it appeared during treatment with neratinib.
The combination of neratinib and everolimus worked in cell lines, organoids derived from patients' tumors, and in mice carrying the mutant HER2 gene. The next step will be to test this combination of the two drugs in humans.
The authors hope that strengthening therapy with everolimus will allow patients to continue effective treatment with the HER2 inhibitor neratinib.
Article by D.R.Sudhan et al. Hyperactivation of TORC1 Drives Resistance to the Pan-HER Tyrosine Kinase Inhibitor Neratinib in HER2-Mutant Cancers is published in the journal Cancer Cell.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru according to UT Southwestern Medical Center: Researchers discover two-drug combo that halts the growth of cancer cells.