By designing a "nanoparticle" drug delivery system, the UC San Diego team, led by Moores UCSD Cancer Center Director of Translational Research David Cheresh, Ph.D., has identified a way to target chemotherapy to achieve a profound impact on metastasis in pancreatic and kidney cancer in mice.
In a study to be published online the week of July 7 in advance of publication in the Proceedings of the National Academy of Sciences (PNAS), Cheresh, professor and vice chair of pathology, and members of his team report that the nanoparticle carrying a payload of chemotherapy homes in on a protein marker called integrin áíâ3 – found on the surface of certain tumor blood vessels where it is associated with development of new blood vessels and malignant tumor growth.
The team found that the nanoparticle/drug combination didn't have much impact on primary tumors, but stopped pancreatic and kidney cancers from metastasizing throughout the bodies of mice. They showed that a greatly reduced dosage of chemotherapy can achieve the desired effect because the drug selectively targets the specific blood vessels that feed the cancerous lesion and kills the lesion without destroying surrounding tissue. The destruction of healthy tissue is a side-effect when chemotherapy is administered systemically, flooding the body with cancer-killing toxins.
"We were able to establish the desired anti-cancer effect while delivering the drug at levels 15 times below what is needed when the drug is used systemically," said Cheresh. "Even more interesting is that the metastatic lesions were more sensitive to this therapy than the primary tumor."
The study is an example of an initiative that joins researchers from UC San Diego's Health Sciences and the Jacobs School of Engineering to improve health care through innovative technologies. Engineers and oncologists working together designed a nanoparticle – a microscopic-sized particle of 100 nanometers, made of various lipid-based polymers – which delivers the cancer cell-killing drug doxorubicin to the network of blood vessels supporting the tumor that express the áíâ3 protein.
"Doxorubicin is known to be an effective anti-cancer drug, but has been difficult to give patients an adequate dose without negative side effects," Cheresh said. "This new strategy represents the first time we've seen such an impact on metastatic growth, and it was accomplished without the collateral damage of weight loss or other outward signs of toxicity in the patient."
Cancer metastasis is traditionally much more difficult to treat than the primary tumor, and is what usually leads to the patient's death. Because metastasis is more reliant on new blood vessel growth, or angiogenesis, than established tumors are, Cheresh theorized that targeting the anti-cancer drug to the sites of new blood vessel growth has a preferential effect on metastatic lesions.
"Traditional cancer therapies are often limited, or non-effective over time because the toxic side effects limit the dose we can safely deliver to the patient," said Cheresh. "This new drug delivery system offers an important advance in treating metastatic disease."
Debra Kain | EurekAlert!
New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg
Stingless bees have their nests protected by soldiers
24.02.2017 | Johannes Gutenberg-Universität Mainz
In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport
Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...
The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.
The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...
Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...
Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".
Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...
13.02.2017 | Event News
10.02.2017 | Event News
09.02.2017 | Event News
24.02.2017 | Life Sciences
24.02.2017 | Life Sciences
24.02.2017 | Trade Fair News