UCLA (US) bioengineers develop platform that offers personalized approach to treatment. In greater than 90 percent of cases in which treatment for metastatic
cancer fails, the reason is that the cancer is resistant to the drugs
being used. To treat drug-resistant tumors, doctors typically use
multiple drugs simultaneously, a practice called combination therapy.
And one of their greatest challenges is determining which ratio and
combination from the large number of medications available is best
for each individual patient.
Dr. Dean Ho, a professor of oral biology and medicine at the UCLA
School of Dentistry, and Dr. Chih-Ming Ho, a professor of mechanical
engineering at the UCLA Henry Samueli School of Engineering and Applied
Science, have developed a revolutionary approach that brings together
traditional drugs and nanotechnology-enhanced medications to create
safer and more effective treatments. Their results are published in the peer-reviewed journal ACS Nano.
Chih-Ming Ho, the paper’s co-corresponding author, and his team have
developed a powerful new tool to address drug resistance and dosing
challenges in cancer patients. The tool, Feedback System Control.II, or
FSC.II, considers drug efficacy tests and analyzes the physical traits
of cells and other biological systems to create personalized “maps” that
show the most effective and safest drug-dose combinations.
Currently, doctors use people’s genetic information to identify the
best possible combination therapies, which can make treatment difficult
or impossible when the genes in the cancer cells mutate. The new
technique does not rely on genetic information, which makes it possible
to quickly modify treatments when mutations arise: the drug that no
longer functions can be replaced, and FSC.II can immediately recommend a
new combination.
“Drug combinations are conventionally designed using dose
escalation,” said Dean Ho, a co-corresponding author of the study and
the co-director of the Jane and Jerry Weintraub Center for
Reconstructive Biotechnology at the School of Dentistry. “Until now,
there hasn’t been a systematic way to even know where the optimal drug
combination could be found, and the possible drug-dose combinations are
nearly infinite. FSC.II circumvents all of these issues and identifies
the best treatment strategy.”
The researchers demonstrated that combinations identified by FSC.II
could treat multiple lines of breast cancer that had varying levels of
drug resistance. They evaluated the commonly used cancer drugs
doxorubicin, mitoxantrone, bleomycin and paclitaxel, all of which can be
rendered ineffective when cancer cells eject them before they have had a
chance to function.
The researchers also studied the use of nanodiamonds to make
combination treatments even more effective. Nanodiamonds byproducts of
conventional mining and refining operations have versatile
characteristics that allow drugs to be tightly bound to their surface,
making it much harder for cancer cells to eliminate them and allowing
toxic drugs to be administered over a longer period of time.
The use of nanodiamonds to treat cancer was pioneered by Dean Ho, a
professor of bioengineering and member of the UCLA Jonsson Comprehensive
Cancer Center and the California NanoSystems Institute.
“This study has the capacity to turn drug development, nano or
non-nano, upside-down,” he said. “Even though FSC.II now enables us to
rapidly identify optimized drug combinations, it’s not just about the
speed of discovering new combinations. It’s the systematic way that we
can control and optimize different therapeutic outcomes to design the
most effective medicines possible.”
The study found that FSC.II-optimized drug combinations that used
nanodiamonds were safer and more effective than optimized drug-only
combinations. Optimized nanodrug combinations also outperformed randomly
designed nanodrug combinations.
“This optimized nanodrug combination approach can be used for
virtually every type of disease model and is certainly not limited to
cancer,” said Chih-Ming Ho, who also holds UCLA’s Ben Rich Lockheed
Martin Advanced Aerospace Tech Endowed Chair. “Additionally, this study
shows that we can design optimized combinations for virtually every type
of drug and any type of nanotherapy.”
Both Dean Ho and Chih-Ming Ho have collaborated with other
researchers and have validated FSC.II’s efficacy in many other types of
cancers, infectious diseases and other diseases.
Other co-authors were Hann Wang, Dong-Keun Lee, Kai-Yu Chen and
Kangyi Zhang, all of UCLA’s department of bioengineering, School of
Dentistry, California NanoSystems Institute and Jonsson Cancer Center;
Jing-Yao Chen of UCLA’s department of chemical and biomolecular
engineering; and Aleidy Silva of UCLA’s department of mechanical and
aerospace engineering.
The work was supported in part by the National Cancer Institute, the
National Science Foundation, the V Foundation for Cancer Research, the
Wallace H. Coulter Foundation, the Society for Laboratory Automation and
Screening, and Beckman Coulter Life Sciences.