Combination Photodynamic Therapy Has Potential to Eradicate Ovarian Cancer

Treatment uses photodynamic therapy with compounds that make cancer cells vulnerable to reactive oxygen species.

A new combination therapy developed by researchers at Oregon State University has the potential to completely eradicate cancerous tumors and recurrent cancer growth in patients with ovarian cancer.

The latest development in cancer treatment may offer a novel mechanism to address the aggressive and often fatal cancer.

Ovarian cancer has a high mortality rate due to the fact that it oftentimes goes undetected until it has metastasized to the abdomen. Toxicity and cancer-cell resistance can also compromise the effectiveness of radiation and chemotherapy that is often used as a follow-up to surgery.

The new method of combatting ovarian cancer takes existing approaches to photodynamic therapy and makes them significantly more effective by adding compounds that make cancer cells vulnerable to reactive oxygen species, and also reducing the natural defenses of those cells.

“Surgery and chemotherapy are the traditional approaches to ovarian cancer, but it’s very difficult to identify all of the places where a tumor has spread, and in some cases almost impossible to remove all of them,” said Oleh Taratula, an assistant professor in the Oregon State University/Oregon Health & Science University College of Pharmacy.

“Photodynamic therapy is a different approach that can be used as an adjunct to surgery right during the operation, and appears to be very safe and nontoxic. In the past its effectiveness has been limited, but our new findings may make this technology far more effective than it’s ever been before.”

The new approach works by first administering a photosensitizing compound called phthalocyanine to the patient. The compound produces reactive oxygen species that can kill cells when they are exposed to near-infrared light. Additionally, gene therapy is administered to reduce cellular defense against reactive oxygen species.

The phthalocyanine and genetic therapy are both composed of “small, interfering RNA” and are attached to what researchers call “dendrimer-based nanoplatforms,” a nanotechnology approach developed by OSU researchers, which delivers the compounds selectively into cancer cells but not healthy ones.

The new approach allows the near-infrared light to penetrate much deeper into abdominal tissues, making the killing of cancer cells much more effective compared to traditional photodynamic therapies. Photodynamic therapy alone has the potential to allow tumors to regrow after just 2 weeks.

But with the addition of the genetic therapy to weaken the cancer cell defenses, there was no evidence of cancer recurrence in the studied mice. Mice also continued to grow and gain weight, indicating to scientists that there were no obvious side effects to the treatment.

“Cancer cells are very smart,” Taratula said. “They overexpress certain proteins, including one called DJ1, that help them survive attack by reactive oxygen species that otherwise might kill them. We believe a key to the success of this therapy is that it takes away those defensive mechanisms.”

The overexpression of the protein DJ1 is associated with invasion, metastasis, resistance to cancer therapies, and overall cancer cell survival, according to the study. The excess of DJ1 is stopped by the genetic therapy composed of siRNA.

An alternative route to recent advances in photodynamic therapy includes the compound naphthalocyanine which is administered prior to surgery and allows cancer cells to glow and fluoresce when exposed to near-infrared light. This allows surgeons to see which tissue is cancerous and which is not.

There’s no reason that approach couldn’t be combined with the newest advance, Taratula noted, providing multiple mechanisms to improve surgical success and, with minimal side effects, help eradicate any remaining cancer cells that were not completely removed.

The development of these strategies in combatting ovarian cancer will certainly change the face of oncology in addition to the survival rate of patients. With complete eradication of cancerous tumors from mice in the study, it is likely that the new approach will yield much success in the extermination of cancer in patients.