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Fatty spheres loaded with siRNA shrink ovarian cancer tumors in preclinical trial

tumor weight ranging from 44 to 72 percent compared with mice in the control groups. Combining the FAK-silencing liposome with docetaxel boosted tumor weight reduction to the 94-98 percent range.

These results also held up in experiments with ovarian cancer cell lines resistant to docetaxel and to the chemotherapy drug cisplatin.

The FAK-silencing liposome and the liposome with chemotherapy also reduced the incidence of cancer by between 20 and 50 percent in all tested cancer lines.

In addition to its anti-tumor effect, the researchers found that the therapeutic liposome attacked the tumor's blood supply, especially when combined with chemotherapy. By inducing cell suicide (apoptosis) among blood vessel cells, the treatment steeply reduced the number of small blood vessels feeding the tumor, cut the percentage of proliferating tumor cells and increased cell suicide among cancer cells.

Sood and Professor of Molecular Therapeutics Gabriel Lopez-Berestein, M.D., an expert in liposomal therapeutics, cite at least two factors for the success of the anti-FAK liposome.

"This particle is so small, it has no problem getting through the tumor's vasculature and into the tumor," Lopez-Berestein says. The FAK-targeting liposome ranges between 65 and 125 nanometers in diameter. Blood vessels that serve tumors are more porous than normal blood vessels, with pores of 100 to 780 nanometers wide. Normal blood vessel pores are 2 nanometers or less in diameter.

Second, the liposome -- a commercially available version known as DOPC -- has no electrical charge. Its neutrality provides an advantage over positively or negatively charged liposomes when it comes to binding with and penetrating cells.

The next step for the FAK siRNA-DOPC liposome is toxicity testing. "So far it appears to be very well-tolerated," Sood says. "We hope to develop this approach for clinical use in the future."

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Source:University of Texas M. D. Anderson Cancer Center


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