Researchers reveal how drug-filled nanoparticles targeted and killed endometrial cancer cells in mice.
The researchers reveal how they successfully targeted and destroyed endometrial cancer cells in mice with an aggressive form of the disease, by injecting them with nanoparticles loaded with anti-cancer drugs.
Lead researcher Kareem Ebeid — of the Division of Pharmaceutics and Translational Therapeutics at the University of Iowa's (UI) College of Pharmacy in Iowa City — and his team recently reported their results in the journal Nature Nanotechnology.
Endometrial cancer is a cancer that begins in cells of the endometrium, which is the inner lining of the uterus.
Around 61,380 women in the U.S. will be diagnosed with cancer of the uterus in 2017. This includes cancers of the endometrium and the corpus, which is the upper area of the uterus.
The team notes that around 10 percent of endometrial cancer cases are uterine serous carcinoma (USC), also referred to as papillary serous adenocarcinoma, and it is classified as a type 2 endometrial cancer.
Despite being less common, USC is highly aggressive. Most cases of USC have already spread to other areas of the body upon diagnosis, making the disease much harder to treat with existing therapies.
As such, USC prognosis is poor, and the disease accounts for around 39 percent of all endometrial cancer deaths.
The new study from Ebeid and his colleagues, however, might have identified a promising new treatment strategy for USC.
"In this particular study," says Ebeid, "we took on one of the biggest challenges in cancer research, which is tumor targeting. And for the first time, we were able to combine two different tumor-targeting strategies and use them to defeat deadly type 2 endometrial cancer."
Targeting cancer's Achilles heel
In simple terms, the new treatment involves taking two drugs already used for cancer treatment and loading them into nanoparticles, which are tiny particles that can deliver drugs directly to tumors.
Tumors produce blood vessels, which provide them with the oxygen and nutrients they need to grow. However, Ebeid and his team note that these blood vessels are flawed; they contain an abundance of holes. Nanoparticles are able to get into these holes, and this makes them an attractive candidate for cancer treatment.
In this latest study, the team loaded the nanoparticles with the drugs paclitaxel and nintedanib, or BIBF 1120. Paclitaxel is a chemotherapy drug used in the treatment of endometrial, ovarian, and breast cancers, while nintedanib is used to reduce blood vessel growth in tumors.
Additionally, nintedanib is able to target a genetic mutation called loss-of-function p53, which is known to drive chemotherapy resistance in cancer cells.
The team injected the drug-loaded nanoparticles into mouse models of USC. Not only did the treatment reduce tumor growth in the rodents, but it also prolonged their survival.
The researchers explain that once the drug-loaded nanoparticles get through the holes in the tumor blood vessels, nintedanib targets and attacks cells that contain the loss-of-function p53 mutation. This makes the tumor cells more vulnerable to the chemotherapy drug.
"Basically," explains Ebeid, "we are taking advantage of the tumor cells' Achilles heel — the loss-of-function mutation — and then sweeping in and killing them with chemotherapy. We call this a synthetically lethal situation because we are creating the right conditions for massive cell death."
Technique could treat a range of cancers
Further studies are needed to confirm the efficacy of drug-loaded nanoparticles in the treatment of USC, but the researchers believe that their results show promise.
"For 2 decades, the standard therapy for type 2 endometrial cancer has been chemotherapy and radiation," says study co-author Kimberly K. Leslie, professor and chair of the Department of Obstetrics and Gynecology at the UI Roy J. and Lucille A. Carver College of Medicine. "The possibility of a new treatment that is both highly selective and highly effective is incredibly exciting."
What is more, the new technique may not be limited to the treatment of endometrial cancer.
"We believe our research could have a positive impact beyond the treatment of endometrial cancer. We hope that since the drugs used in our study have already been approved for clinical use, we will be able to begin working with patients soon."
Study co-author Aliasger K. Salem, University of Iowa