Researchers Identify New Approach to Administering Cancer Radiation

Researchers from Osaka University and the University of Heidelberg are experimenting with a new approach to radiation therapy that may effectively treat pancreatic cancer patients while causing minimal damage to surrounding tissues. This team’s proof-of-concept study was published recently in The Journal of Nuclear Medicine.

Pancreatic cancer is a leading cause of cancer mortalities, with chemotherapy and radiation therapy treatments often failing to have success in patients. These treatments also come with unwarranted side effects as well, such as toxicity and damage to healthy tissues and organs surrounding the cancer. These treatments work in part by inhibiting mitosis, or the proliferation of cells through division. Although it is beneficial to stop cancer cells from dividing, these treatments yield negative side effects by stopping the mitosis in healthy cells as well.

“With traditional anti-cancer therapies, there’s a tradeoff between efficacy against cancer cells and off target effects in non cancerous cells,” explained lead author Tadashi Watabe, researcher in nuclear medicine and tracer kinetics at Osaka University Graduate School of Medicine. “We’re focused on finding ways to re-balance this tradeoff in radiotherapy, by increasing the dose of radiation delivered to cancer cells while keeping it localized to those cells as much as possible.”

This targeted therapy can be achieved through a molecule that travels directly to the tumor site to administer treatment upon injection. In this collaborative study, the researchers created such a homing molecule that was designed to directly target cancers of the pancreas.

“We used a molecule with an isotope that emits alpha particles,” said Watabe. “These particles travel a shorter distance than the beta particles emitted by traditional isotopes, which means their off-target effect is limited. Our molecule binds to a protein called FAP, which is found almost exclusively on stroma cells that surround pancreatic tumors and various types of cancers. Together, this allows us to target a high energy dose of radiation directly to the site of the tumor.”

Stromal cells make up the microenvironment that surrounds tumors and play a significant role in the growth, progression, and transition of malignancy. The stroma surrounding malignancies can often block cancer treatments from working effectively, however, this experimental approach appears to circumvent this.

In the researchers’ proof-of-concept study, they injected this FAP-binding agent into mice with human pancreatic cancer grafted into their skin. They found that animal models of this tumor showed significant reductions in growth with no effect on body weight. This was indicative of minimal side effects of their treatment.

“We are very encouraged by these initial results. We think the approach has enormous therapeutic potential, particularly for patients with pancreatic cancer who’ve exhausted their other treatment options,” Watabe claimed. “What’s especially exciting is that our method of targeting the stroma can in principle work against many other types of cancer. We think this could represent a new path forward in radiation therapy.”

The authors of the publication concluded that the experimental treatment “could be used in theranostics for the treatment of FAP-expressing pancreatic cancer,” and that “alpha therapy targeting FAP in the cancer stroma is effective and will contribute to the development of a new treatment strategy.”