Scientists create “drug-like” chemical that may inhibit pancreatic cancer stem cells

John R. Cashman, Ph.D.

Supreme Court justice Ruth Bader Ginsburg’s death this past week after battling stage 4 pancreatic cancer is a grim reminder of how aggressive the disease can be. In fact, pancreatic cancer will soon be the second leading cause of cancer-related death for individuals in the United States. Unfortunately, it is known to be highly resistant to treatments that are currently available.

With the aid of CIRM-funding, John R. Cashman, Ph.D., along with a team of researchers at the Human BioMolecular Research Institute and ChemRegen, Inc. have developed a “drug-like” chemical that may change that. The newly created compound, PAWI-2, was tested on pancreatic cancer stem cells in a laboratory setting. The compound works by activating apoptosis, a process that tells the cells when to stop dividing and influences cell death.

Under the microscope, the team of researchers found that PAWI-2 successfully inhibited the growth of these cancer stem cells. In addition to this, the team analyzed if PAWI-2 had any effect on existing pancreatic cancer treatments, specifically erlotinib and trametinib. What they found was that their “drug-like” chemical improved the effectiveness of both of these anti-cancer drugs.

In a press release, Dr. Cashman explained the significance that PAWI-2 could play for pancreatic cancer treatments.

“We need to develop effective new medications for drug resistant pancreatic cancer. Using a non-toxic small molecule like PAWI-2 to stop pancreatic cancer either by itself or in combination with standard of care chemotherapy is very appealing.”

The full paper, published in Investigational New Drugs, can be accessed here.

Blocking pancreatic cancer stem cells

John Cashman

Cancer stem cells are one of the main reasons why cancers are able to survive surgery, chemotherapy and radiation. They are able to hide from those therapies and, at a future date, emerge and spread the cancer in the body once again.

Jionglia Cheng, PhD.

Jionglia Cheng, PhD., the lead author of a new CIRM-funded study, says that’s one of the reasons why pancreatic cancer has proved so difficult to treat.

“Pancreatic cancer remains a major health problem in the United States and soon will be the second most common cause of mortality due to cancer. A majority of pancreatic cancer patients are often resistant to clinical therapies. Thus, it remains a challenge to develop an efficacious clinically useful pancreatic cancer therapy.”

Dr. Cheng, a researcher with ChemRegen Inc., teamed up with John Cashman at the Human BioMolecular Research Institute and identified a compound, that seems to be effective in blocking the cancer stem cells.

In earlier studies the compound, called PAWI-2, demonstrated effectiveness in blocking breast, prostate and colon cancer. When tested in the laboratory PAWI-2 showed it was able to kill pancreatic cancer stem cells, and also was effective in targeting drug-resistant pancreatic cancer stem cells.

In addition, when PAWI-2 was used with a drug called erlotinib (brand name Tarceva) which is commonly prescribed for pancreatic cancer, the combination proved more effective against the cancer stem cells than erlotinib alone.

In a news release Dr. Cheng said: “In the future, this molecule could be used alone or with other chemotherapy albeit at lower doses, as a new therapeutic drug to combat pancreatic cancer. This may lead to much less toxicity to the patient,”

The study is published in the journal Scientific Reports.