Paclitaxel plus nintedanib overcomes chemotherapy-resistance in endometrial cancer.
Nanoparticles have been a promising drug delivery method for various forms of cancer and other diseases that require a highly-targeted therapy.
Delivering a combination of cancer drugs via a targeted nanoparticle may provide a more potent treatment against a deadly form of endometrial cancer, according to a study published by Nature Nanotechnology.
In the study, chemotherapy and a drug that combats drug-resistant cells were loaded into nanoparticles in an attempt to create a highly-effective approach to treating cancer.
The authors said this novel treatment could improve the survival rate among 6000 women who are diagnosed with type 2 endometrial cancer each year, according to the study. Additionally, these findings further the development of more targeted cancer treatments.
“In this particular study, we took on one of the biggest challenges in cancer research, which is tumor targeting,” said lead researcher Kareem Ebeid. “And for the first time, we were able to combine two different tumor-targeting strategies and use them to defeat deadly type II endometrial cancer. We believe this treatment could be used to fight other cancers, as well.”
Targeted therapies have become more common for cancer because it does not expose the entire body to harmful drugs. The small size of nanoparticles has also sparked interest due to the potential of an improved drug delivery mechanism. Since tumors grow rapidly, their blood vessels are full of holes that nanoparticles can fit through to deliver the treatment, according to the study.
The authors loaded the nanoparticles with paclitaxel chemotherapy and nintedanib, a newer drug used to limit blood vessel growth. Nintedanib also targets tumors with a p53 mutation, which makes cancer cells drug resistant, according to the study.
Cells that experience a mutation called Loss of Function p53 are stuck in limbo, meaning that they cannot be killed by chemotherapy during cell division, according to the authors. Chemotherapy-resistant cancers are notoriously difficult to treat and have poor outcomes. However, the addition of nintedanib forces cells to divide, allowing them to be killed by chemotherapy, according to the authors.
“Basically, we are taking advantage of the tumor cells’ Achilles heel—the Loss of Function mutation—and then sweeping in and killing them with chemotherapy,” Ebeid said. “We call this a synthetically lethal situation because we are creating the right conditions for massive cell death.”
The authors said that their findings could be translated to other cancers that have the Loss of Function p53 mutation, including ovarian and lung cancers.
“We believe our research could have a positive impact beyond the treatment of endometrial cancer,” said corresponding author Aliasger K. Salem, PhD. “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.”
The prevalence of endometrial cancer has been increasing in the United States over the past few years. Type 1 endometrial cancer accounts for 80% of cases, but type 2 is much more aggressive and accounts for nearly 40% of endometrial cancer deaths, according to the study.
“For 2 decades, the standard therapy for type II endometrial cancer has been chemotherapy and radiation,” said Kimberly K. Leslie, MD. “The possibility of a new treatment that is both highly selective and highly effective is incredibly exciting.”