Researchers in Singapore have discovered how cancer gradually blocks the effectiveness of HER2 drugs, and have found an existing, clinically approved drug, that can stop this.
Approximately 20-25% of women with breast cancer are HER2+ve. Before Herceptin came along, there really was no medical treatment for this cancer. However, the wonder drug is not so wonderful. It can lose effectiveness at two to five years depending on the patient. A ‘daughter of Herceptin’ - Perjeta - was created by Roche to extend the performance but results are ultimately not much better.
Now researchers, led by Professor Yu of the Genomic Institute in Singapore (GIS), have explored the reason why the cancer beats the drug(1). Apparently, a third of HER2+ve patients' breast cancers have low levels of PPP2R2B. And this fall in levels increasingly prevents HER2 drugs working.
This suppression is caused by a compound promoted by cancer cells, namely EZH2. The researchers then found that an existing drug, currently called EPZ-6348, is capable of blocking EZH2, so allowing drugs like Herceptin and Perjeta to keep working longer.
Chris Woollams, former Oxford University biochemist said, “I am amazed that I stumbled across this piece of research and it is not being widely published in Europe and America. Oncologists already go outside Clinical Trial guidelines to add drugs to drugs; Dexamethasone, Propranolol and Metformin all spring to mind. Here is something clinically available and it would be relatively easy to mount a short-term real life trial. A while back we covered how off-label drug Ivermectin could extend the life of Paclitaxel and Adriamycin. Ignoring research like this brings into question whether oncologists really believe in their drugs in the first place. If you believed in it, you’d want it to work as long as possible.”
Go to: Ivermectin overcomes drug resistance, extendsdrug effectiveness
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Reference
- Yi Bao et al. EZH2-mediated PP2A inactivation confers resistance to HER2-targeted breast cancer therapy, Nature Communications (2020). DOI: 10.1038/s41467-020-19704-x