SINGAPORE: Local scientists have discovered a way to use an alternative medicine to counter resistance to a form of targeted therapy that is used to treat HER2-positive breast cancer patients.
Medications that are often used to treat patients with this condition often stop working after a while and cause a relapse.
Researchers from the Singapore Cancer Science Institute at the National University of Singapore, the Singapore Genome Institute under the Agency for Science, Technology and Research and the Singapore National Cancer Institute (NCIS), along with its international research collaborators in Denmark, we have analyzed why this happened.
The team, led by Professor Lee Soon Chin of NCIS Singapore and Professor Yu Qiang of GIS, focused on a protein called HER2 (receptor 2 of human epidermal growth factor), which stimulates cancerous cell growth. mammary glands when presented in excessive amounts.
Drugs targeting the HER2 protein often became ineffective, although scientists could not figure out why.
To decipher the mechanisms of cancer resistance to anti-HER2 therapy, the team used existing data from a biochemical database along with tumor samples from 29 patients enrolled in a clinical trial at NCIS.
They focused on an enzyme subunit known as PPP2R2B, which suppresses cancer by making chemical modifications in a signaling pathway.
Breast cancers that did not respond well to anti-HER2 therapy tended to have lower levels of PPP2R2B enzyme.
In fact, the activity of the enzyme PPP2R2B was suppressed by another enzyme known as EZH2.
Plans to conduct a clinical trial to test the effectiveness of combining both drugs to treat HER2-positive breast cancer patients.
In addition, the enzyme PPP2R2B could be used as a potential predictive marker to identify patients who may be resistant to standard anti-HER2 therapy and may benefit from additional therapy.
Professor Lee, who is also chief and senior consultant in the NCIS Department of Hematology-Oncology, said HER2-positive breast cancer comprises 20 to 25% of all breast cancers.
“Despite initial efficacy, resistance to anti-HER2 therapy develops almost invariably in patients with advanced cancer and will eventually succumb to the disease,” he noted.
“This study provides information on why anti-HER2 drugs ultimately fail and offers a solution to restore sensitivity to anti-HER2 treatment, which can prolong patient survival.”