Nanoparticles Improve Head and Neck Cancer Treatment
PI3K inhibitors loaded into nanoparticles provided targeted treatment for head and neck cancers.
The creation of novel treatments for head and neck cancers have long been hindered by side effects from targeted drugs. The cancers are known to be susceptible to PI3K inhibitors, which block cell proliferation resulting from a mutated PIK3CA gene; however, the drugs can cause fatigue and high blood glucose levels.
In a new study published by Nature Communications, the authors developed a new approach to deliver PI3K inhibitors to the tumors through nanotechnology. For this approach, drugs are loaded into nanoparticles, which then target the protein P-selectin in the blood vessels around the tumors. This method causes the drug to aggregate at the site of the tumor.
“We showed in mice that we could achieve the same antitumor effect even using a dose seven times less than what would normally be given systemically,” said lead study author Maurizio Scaltriti, PhD. “We’re optimistic and excited about getting this into the clinic.”
The investigators believe that this method is a promising treatment for head and neck cancers, since P-selectin expression increases when exposed to radiation. Since radiation is the standard treatment for these cancers, the approach would lead to increased tumor toxicity.
Previously, the investigators developed nanoparticles out of fucoidan, which is extracted from seaweed and naturally targets P-selectin. The protein captures nanoparticles, which causes them to stay at the tumor site, and deliver the drug.
In the new study, the investigators created a model to bring the new technology to a clinical setting. Currently, PI3K inhibitors are being explored in a variety of cancers, since the PI3K pathway is commonly mutated. The compound BYL719 was used in the study, and is also being explored in phase 3 studies of breast cancer.
The authors found that nanoparticles loaded with BYL719 inhibited cancer cell growth. In animal models of the disease, the investigators reported no rise in glucose levels.
“When you give a PI3K inhibitor using conventional methods — intravenously or by mouth, so that it goes throughout the body — you see the PI3K pathway being suppressed for a while, but then it goes back up after a few hours as the drug is cleared from the system,” Dr Scaltriti said. “With nanoparticles, you see this signaling pathway inhibited even after 24 hours, and the blood glucose levels don’t rise. The only explanation is that the drug is accumulating at the tumor.”
The investigators are now testing various approaches to translate the method to humans. The authors plan to determine how various drugs can be packed inside the nanoparticles, which affects how the molecules are released at the tumor site, according to the study.
“PI3K inhibitors are currently at a delicate stage,” Dr Scaltriti said. “Everybody knows they are active against cancer but also that they are difficult to tolerate. This could be one way to shift the balance toward the activity side.”
The investigators said they are positive that exploring this approach further will be supported by oncologists, since there are few options after the initial treatment is ineffective. Depending on safety approval for fucoidan and collaboration with a pharmaceutical company, the authors believe the method could be tested in humans within 3 years.
“In 2017, patients don’t just want to be treated or cured, they also want to have a good quality of life,” Dr Scaltriti concluded. “This could be one way to address it, by giving smaller amounts of the drug that all go to the right spot.”