Urszula Waśko from Columbia University is participating in work on a drug that can block the development of pancreatic cancer. It is a cancer that is still very difficult to cure. The results of experiments on mice are promising. The first phase of clinical testing of the new drug in humans has begun.
Steve Jobs, Anna Przybylska, Patrick Swayze. They left too soon, in their prime. They died of pancreatic cancer.
The pancreas is a small organ in the abdominal cavity that produces hormones that regulate blood sugar levels and digestive enzymes. Pancreatic cancer is not very common, but it is extremely difficult to treat. It does not produce typical symptoms for a long time. At the beginning of the disease, patients may experience abdominal and back pain, nausea and loss of appetite. They lose weight and have problems with bowel movements.
– Most patients find out that they have pancreatic cancer at a very advanced stage. One of the characteristic symptoms is jaundice, which causes the skin and eyeballs to turn yellow. Patients may also have darker urine and lighter stools, says Professor Kavitha Ramchandran, an oncologist at Stanford University.
Once cancer is diagnosed, it is often difficult to operate. The pancreas is hidden behind the stomach and is adjacent to important organs and blood vessels, and cancer often grows between them. In turn, when chemotherapy is administered, the challenge is to ensure that the drug reaches the tumor at all.
In the US, the five-year survival rate from diagnosis is 12.5 percent
– We have an environment of this tumor that is full of immune cells that protect the tumor against any response of the body to neutralize it. Because it is such a compact and dense tumor, there are not many blood vessels there, and drugs are delivered to the tumors through blood vessel transport – explains Urszula Waśko, a doctoral student in the Department of Pharmacology at the Irving Medical Center at Columbia University.
Pancreatic cancer has a high mortality rate. In the United States, the five-year survival rate from diagnosis is 12.5 percent. In Poland it is even lower, and each year about three and a half thousand new cases are registered.
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Patients are still waiting for help, which is why this latest publication in the journal “Nature” was received with such great hope. Revolution Medicines from California has developed an inhibitor, i.e. a molecule that blocks the activity of the mutant RAS protein present in cancer cells. This mutated RAS protein is the driving machine that causes cells to multiply uncontrollably. The new drug blocked the activity of the protein and the cancer stopped growing.
The drug spares healthy cells
– We saw cancer cells die. We saw that it worked in cells on a plate, in mice. We saw that these tumors shrank in response to the inhibitor. As for mice, all mice that I tested personally responded. I saw that either the tumor had stabilized or was shrinking – says Waśko.
Urszula Waśko works in a laboratory specializing in research on pancreatic cancer. She graduated in biotechnology from the University of Wrocław and is currently completing her PhD at Columbia University in New York. She checked the effectiveness of the new drug on various cancer models and coordinated cooperation with other scientists. The drug was tested by several different teams in the United States.
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– Because there were so many labs there at the same time, someone had to take control of it all. This became my PhD project, so I mainly did this research in our laboratory. All the results that came out of our lab were created by me – says Waśko.
Scientists observed that the drug caused the death of cancer cells in the tumor but did not damage healthy tissue. – Four hours after administering the drug, we collect tissue from the mice and then perform histological analysis. We see that the entire tumor is covered with dying cancer cells, but if we take normal tissue, intestine or mouse skin, we do not see these dying cells, says Waśko.
The drug is currently in the first phase of clinical testing in humans
In some cases, scientists observed tumor recurrence. Over time, resistance to the drug developed in the cells. – At a certain stage, these cells “learn” as if these drugs also stopped working. These proteins, which have been blocked thanks to this mechanism of a very refined substance, change their shape and this substance does not fit these proteins – says Dr. Wiesław Bal from the National Institute of Oncology in Gliwice.
We asked Polish specialists to comment on the publication in Nature and the results of research on the new drug. They are clearly impressed.
– In 70 percent of cases there was a very clear response to treatment. This treatment was long-term and a mechanism of resistance was identified. It has been identified how cancer cells defend themselves against this drug. Perhaps this will be the huge progress we are waiting for – comments Professor Piotr Wysocki, an oncologist from the University Hospital in Krakow.
The drug is currently in the first phase of clinical testing in humans. Scientists check how well it is tolerated by patients and what dose would be optimal – both effective and safe. The research and possible market approval procedure will take several years.
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