New treatment options for patients with HER2 .-positive breast cancer
It’s important to remember, Shagisultanova says, that HER2 and PI3K are necessary for cell growth and development — the type of growth that takes place in normal tissue. However, “when it becomes abnormally activated, all the check and balance systems go out of balance, and that’s when the cancer begins.”
HER2 is a protein present in about 20% of breast cancers. HER2-positive breast cancers tend to be more aggressive than other types of breast cancer, although treatments designed to specifically target HER2 have been shown to be very effective. Many treatments involve blocking HER2 growth signals.
“Since we discovered the HER2 inhibitor, the life expectancy of patients with HER2-positive breast cancer has improved a lot, because we were able to stop one of the main causes of cancer,” says Shagisultanova. the main cause of this cancer. “If we just use chemotherapy and don’t stop HER2, cancer cells divide faster than we can kill them, even with powerful chemotherapy. But once we block the increased signal growth of HER2, the combination of that HER2 blocker and chemotherapy can kill tumor cells and cure patients with HER2-positive early breast cancer or prolong survival for patients with HER2-positive tumors. counted with metastatic HER2.”
However, approximately 30% of HER2-positive patients also have PIK3CA mutations. Because the PI3K protein is directly connected to the HER2 receptor, “if it is mutated and already activated, to the extent that you block the upstream HER2 growth signal, PI3K will still send growth signals downstream and renders our blockade useless,” explains Shagisultanova. “PI3K will tell tumor cells to grow.”
Development of a PIK3CA . inhibitor
Now that the evidence shows that PI3K promotes treatment resistance in HER2-positive breast cancer, one of the next important research focuses will be the development of PI3K inhibitors.
“It is difficult to develop effective inhibitors of this molecule because PI3K is connected to many growth factor receptors,” said Shagisultanova. “In early trials, we found that when you block PI3K, the insulin signal tries to counteract this blocking and blood sugar goes up. So one of the side effects is diabetes. and we don’t want to expose cancer patients to other conditions during cancer treatment.”
In 2019, a second-generation PI3K inhibitor without high levels of toxicity was developed. Through cell and animal models performed in her laboratory, Shagisultanova was able to show that the recently approved PI3K blocker in combination with a HER2 blocker caused tumors to regress,” very very encouraging,” she said. “We found that it led to the suppression of tumor growth.”
“What we’re trying to do is cut off all the pathways for tumor cells to grow,” explains Shagisultanova. “We hope that this combination of PI3K and HER2 inhibitors will show significant results for patients with this aggressive type of breast cancer.”