Threefold approach to improving anticancer drug Biomedical engineers at Duke University have developed a method to address failures in a promising anticancer drug, bringing together tools from genome engineering, protein engineering and biomaterials science to improve the efficacy, accuracy and longevity of certain cancer therapies. Their research has been published in the journal Science Advances.
M
to the therapy. Now, using a combination of three tools — a highly potent protein drug, a ‘depot’ that allows for sustained release of the drug and CRISPR/Cas9based gene editing to pinpoint the cause of resistance
ore than 20 years ago, researchers
to the drug — the Duke team has demonstrated how
discovered that the protein drug TRAIL, short for
they could provide a solution to these problems and
TNF-related apoptosis-inducing ligand, could
give protein-based anticancer ‘biologics’ like TRAIL
effectively kill cancer cells without harming healthy
that failed in the clinic a second chance.
cells — at least, in the lab. TRAIL works by binding
“The real significance of this research for me is the
to specific protein receptors on cancer cells, called
true cross-disciplinary nature of it,” said first author
death receptors, sending a signal that causes the
Mandana Manzari, now a postdoctoral researcher at
cells to self-destruct. Although initial experiments
the Memorial Sloan Kettering Cancer Center. “This is
showed the drug worked in a variety of cancer cell
really the first example I’ve seen where we’re bringing
lines, including melanoma, lymphoma, pancreatic,
in pharmacology, drug delivery and genomics to
prostate, lung, colon and breast cancer, TRAIL and
pinpoint the exact circumstances that cause a biologic
similar drugs surprised researchers by showing limited
to fail and then develop solutions.”
success in clinical trials.
The first step of the process involved addressing
After more study, scientists pinpointed three
TRAIL’s limited potency. Typically, cells have multiple
reasons why the promising drug failed: TRAIL wasn’t
death receptors, but a specific receptor called death
potent enough, the drug was being cleared from the
receptor 5 (DR5) is more prevalent in certain cancer
body too quickly and some cancer cells were resistant
cells. TRAIL, a three-part protein, binds to DR5 and
32 | LAB+LIFE SCIENTIST - Dec 2019/Jan 2020
www.LabOnline.com.au | www.LifeScientist.com.au