A new study shows that a drug derived from a protein found in the malaria parasite stopped chemotherapy-resistant bladder cancer tumors growing in mice. The researchers say that the finding could lead to much-needed new treatments for cases of bladder cancer that do not respond to standard therapy.
The international team behind the study - which is published in the journal European Urology - includes members from the University of British Columbia (UBC) in Vancouver, Canada.
Senior author Mads Daugaard, a senior research scientist at the Vancouver Prostate Centre and the Vancouver Coastal Health Research Institute, and an assistant professor of urologic science at UBC, says that this the first time that the idea of using malaria proteins to treat cancer has been put "into a direct clinical context."
"There is a massive clinical need to find new treatments for bladder cancer and we saw an opportunity to target this disease with our new malaria drug," he adds.
The bladder is a hollow organ in the pelvis that stores urine before it leaves the body. Muscle tissue in the walls of the bladder allow it to stretch to accommodate urine.
Bladder cancer arises when cells in the bladder grow out of control. As more cancer cells grow, they can develop into a tumor and spread to neighboring tissue and other parts of the body.
The American Cancer Society estimate that there will be approximately 79,030 new cases of bladder cancer and 16,870 deaths from the disease in the United States during 2017.
Malaria protein can target cancer tumors
Although it is the fifth most common cancer in the U.S., bladder cancer has the highest per patient cost. There is only one chemotherapy treatment for muscle-invasive bladder cancer (MIBC) - a predicament that has changed little in 20 years, say the researchers.
- Bladder cancer accounts for around 5 percent of new cancer cases in the U.S.
- It is more common in men than in women.
- The average age at diagnosis is 73.
The standard of care for MIBC is "cisplatin-based neoadjuvant chemotherapy." However, only around 40 percent of patients show a major response to this first-line treatment and therefore, "second-line treatment options for MIBC are currently in great demand," note the authors in their paper.
The new study builds on previous work by Prof. Daugaard and co-investigator Ali Salanti, a professor in the Center for Medical Parasitology at the University of Copenhagen in Denmark.
That research showed that a protein called VAR2CSA - normally found in the malaria parasite Plasmodium falciparum - could deliver cancer drugs into tumors.
The researchers say that the protein attaches to a particular group of sugar chains - called "oncofetal chondroitin sulfate glycosaminoglycan chains (ofCS)" - that are normally found only in cancer tumors and placental tissue.
Because cisplatin-resistant bladder cancer has unusually high levels of ofCS, Prof. Daugaard and colleagues decided to explore the potential for using VAR2CSA as a basis for treating this form of the disease.
Effect of combination drug was dramatic
For the new study, the team used mice implanted with tumors taken from human patients with highly aggressive forms of MIBC.
The researchers developed an experimental drug that combined certain domains of the VAR2CSA malarial protein with three cell-toxic compounds derived from a marine sponge.
When they treated the mice with the combination drug, there was a dramatic effect: 80 percent of the mice survived for more than 70 days, whereas none of the mice in three other control groups that did not have the combination therapy survived.
The team is now working on a way to produce the drug on a larger scale for use in clinical trials. Profs. Daugaard and Salanti will be leading the work at a company that they started.
"We're very excited by these results because it shows that we are on our way to developing a completely new treatment option for lethal bladder cancer. It has the potential to have a tremendous impact on patient care."
Prof. Mads Daugaard