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New HER2 inhibitor shows promise in Roswell Park study

The HER2 protein, which encourages the growth of cancer cells, is present in about 20 percent of all breast cancers. While HER2-positive breast cancers tend to be very aggressive, today the prognosis is generally very good, thanks to the introduction of HER2 inhibitors such as trastuzumab (brand name Herceptin).

However, not all HER2-positive breast cancers respond to existing HER2 inhibitors.

In a study published recently in Science Translational Medicine, Roswell Park Comprehensive Cancer Center researchers report that a new anticancer agent, PEPD-G278D, has the potential to overcome that drug resistance.

The agent is a new HER2 inhibitor that operates on several fronts.

The Roswell Park team, led by Dr. Yuesheng Zhang, professor of oncology in the departments of Pharmacology & Therapeutics and Cancer Prevention & Control, concluded based on results of a preclinical study that the agent – a modified human protein — binds to HER2 and strongly inhibits its activity in cancer cells.

At the same time, the team observed that PEPD-G278D shows additional actions not seen with other HER2 inhibitors:

  • It improves the efficacy of the chemotherapy drug paclitaxel (brand names Taxol and Onxal).
  • It prevents HER2 from being protected by the protein mucin 4, making the cancer cells more vulnerable to treatment.
  • It prevents HER2 from interacting with other cell surface receptors, which contribute to the growth of cancer cells.
  • It decreases production of epidermal growth factor receptor, which strengthens drug resistance in HER2-positive breast cancer.

“Our results show that HER2 remains a critical target in drug-resistant HER2-positive breast cancer and that PEPD-G278D is a promising agent for overcoming drug resistance in this disease,” study first author Lu Yang, a research associate in Zhang’s lab, said in a news release.

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