Intraoperative ovarian cancer treatment based on the combinatorial effect of a targeted photodynamic therapy (PDT) associated with suppression of the DJ-1 protein, one of the key players in the ROS defense of cancer cells. Ovarian cancer tumors exposed to a single dose of combinatorial therapy were completely eradicated from the mice and the treated animals showed no evidence of cancer recurrence.
A combination of techniques by Oregon State University researchers achieved complete cancer cell elimination with no regrowth of tumors. It may offer a novel mechanism to address this aggressive and often fatal cancer that kills 14,000 women in the US each year. Ovarian cancer has a high mortality rate because it often has metastasized into the abdominal cavity before it’s discovered. Toxicity and cancer-cell resistance can also compromise the effectiveness of radiation and chemotherapy that’s often used as a follow-up to surgery.
They took 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. “It can be used as an adjunct to surgery right during the operation, and appears to be very safe and nontoxic,” Taratula said.
METHOD: patient is first given a photosensitizing compound called phthalocyanine, which produces reactive oxygen species that can kill cells when they are exposed to near-infrared light. In addition, a gene therapy is administered that lowers the cellular defense against reactive oxygen species.
Both the phthalocyanine and genetic therapy, composed of “small, interfering RNA,” are attached to what researchers call “dendrimer-based nanoplatforms,”. It delivers the compounds selectively into cancer cells, but not healthy cells.
Compared to existing photodynamic therapies, this approach allows the near-infrared light to penetrate much deeper into abdominal tissues, and dramatically increases the effectiveness of the procedure in killing cancer cells. Using photodynamic therapy alone, some tumors in laboratory animals began to regrow after 2 weeks. But combinatorial genetic therapy weakens the cancer cell defenses, and there was no evidence of cancer recurrence. Mice receiving the gene therapy also continued to grow and gain weight, indicating a lack of side effects.
“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.” Overexpression of DJ1, is associated with invasion, metastasis, resistance to cancer therapies, and overall cancer cell survival. That excess of DJ1 is silenced by the genetic therapy composed of siRNA.
This could build upon some other recent advances in photodynamic therapy, in which naphthalocyanine could be administered prior to surgery, causing the cancer cells to “glow” and fluoresce when exposed to near-infrared light, ie gives a road map for surgeons to follow.
http://oregonstate.edu/ua/ncs/archives/2015/aug/advance-photodynamic-therapy-offers-new-approach-ovarian-cancer
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