The National Cancer Institute launched its Alliance for Nanotechnology in Cancer with the goal of using nanomedicine to change the way cancer is treated.
In 2004, the National Cancer Institute (NCI) launched its Alliance for Nanotechnology in Cancer, with the goal of using nanomedicine to change the way cancer is treated. Ten years later, the promise of nanotechnology has not yet been fulfilled.
When the initiative was founded, there was one approved nano-enabled cancer treatment: doxorubicin liposome injection, marketed at the time as Doxil, which encapsulates a toxic chemotherapy agent into a nanometer-scale liposome that eludes the immune system’s defenses and delivers a portion of the drug directly to the tumor.
In 2005, the Food and Drug Administration (FDA) approved Abraxane (albumin-bound paclitaxel), a form of paclitaxel that uses a nanoparticle system to reduce drug delivery time from three hours to a half hour for advanced breast cancer. However, there is some debate over whether Abraxane can be termed a “nanoparticle,” as its 130-nm size does not fit the FDA’s definition of nanotechnology, which limits particles to 100 nm—a difference of about the size of a single virus.
In 2012, the FDA granted accelerated approval to Marqibo (vincristine sulfate liposome injection) for the treatment of Philadelphia chromosome-negative acute lymphoblastic leukemia. And in 2013, the FDA approved a combination of Abraxane and gemcitabine to treat late-stage pancreatic cancer.
Other than these few notable successes, nanomedicine’s potential in treating cancer remains strong but not yet fully realized.
“There are many different therapeutic formulations using nanoparticles in different stages of clinical trials, from phase 1 to phase 3, and the number of these trials is continuously increasing,” says Piotr Grodzinski, director of the Alliance for Nanotechnology in Cancer at the NCI.
Cancer’s ability to develop resistance is another target of nanomedicine.
Among the liposomal nanomedicines now in late-phase trials is CPX-351, a treatment for high-risk acute myeloid leukemia, which uses nano-encapsulation to maintain an ideal ratio of two chemotherapy drugs, cytarabine and daunorubicin. “This is the first time a therapy involving two drugs in one carrier has advanced this far in clinical trials,” says Frank Szoka, a professor of biopharmaceutical sciences and pharmaceutical chemistry at the University of California, San Francisco, and one of the developers of liposomal doxorubicin.
Nanomedicine is used to deliver agents that are difficult to give in their free form or are very toxic, Grodzinski explains. For example, the injectable targeted agent Kyprolis (carfilzomib), approved for previously treated multiple myeloma, metabolizes rapidly in plasma. “Protecting it in a nanoscale carrier can extend its half-life and give it the potential to attack the tumor locally,” Szoka says.
Nanotechnology isn’t just about delivering chemotherapeutic agents. A medical device that uses iron oxide particles to locally elevate the temperature within the tumor and eradicate tumor cells has been approved in Europe and is being studied in the U.S. Nanoscale tools for diagnosing and staging cancer are also moving forward.
Cancer’s ability to develop resistance is another target of nanomedicine. California Institute of Technology chemist James Heath has developed a way to analyze tumors at the single-cell level. He says doing so allows researchers to “directly extract a model of the cancer signaling pathway—something you can’t do at a larger scale.” When the researchers hit that single tumor cell with a new drug, “we can see how its signaling system is rerouted to avoid the ‘roadblock’ of the drug, just like traffic reroutes itself on a freeway when an off-ramp is closed,” he says. “That gives us predictions on what sort of combinations of therapies we can give to a patient that will both treat the tumor and anticipate the growing resistance.”
But the reason so much of cancer nanomedicine remains frustratingly “on the verge” is its inherent complexity. “Nano formulations have to be engineered one by one,” Szoka says. “Essentially, you are building a small machine. This means that going from an academic study to a clinical study is much harder—akin to taking your car from your garage to the Daytona Speedway.”