Discovered a new class of drugs that can successfully treat a rare form of leukemia and hold promise to be effective therapies for pancreatic and lung cancer as well as mesothelioma.

Ira Pastan, M.D.

Listen to Ira Pastan discuss his work:

In 2018, the Food and Drug Administration approved a breakthrough drug to treat a rare but deadly form of leukemia in patients who have few other treatment options.  

This medication, now marketed by Astra Zeneca under the name Lumoxiti, is the result of decades of research by Dr. Ira Pastan of the National Cancer Institute, whose discovery has led to a class of drugs that can kill cancer cells while leaving healthy cells intact and save patients’ lives. 

“Dr. Pastan is now building on the success of this new class of drugs he developed called Recombinant Immunotoxins that could also be effective against solid tumors such as pancreatic and lung cancer, and mesothelioma, in addition to leukemia,” said Thomas Misteli, director of cancer research at the National Institutes of Health.  

Dr. Michael Gottesman, deputy director for Intramural Research at NIH, said Pastan’s “creative and innovative approach” could be a game changer that results in a brand-new way to treat cancer. 

When Pastan first came up with his idea of using bacterial toxins for treating cancer, “it was not popular and most immunologists said it would never work, but he has taken this idea and this dream and turned it into reality,” Misteli said.  

The rare form of cancer Lumoxiti treats is known as hairy cell leukemia. Patients generally respond well to existing therapies like chemotherapy, but 30% to 40% relapse after five to 10 years due to resistance to cancer drugs. No other options had previously been available.  

“Lumoxiti fills an unmet need for patients with hairy cell leukemia whose disease has progressed after trying other FDA-approved therapies,” Dr. Richard Pazdur, the FDA director of the Oncology Center of Excellence, said in a statement at the time the drug was approved.  

Reflecting on the FDA approval, Pastan, who at 88 is still working, said, “I am very excited about that. It is how things usually begin. Once a drug is approved for one kind of cancer, you try to make it useful for treating other types of cancer.”  

Pastan’s research focuses on bacterial protein toxins that are toxic to human and other animal cells. 

He worked to direct the biotoxin to target cancer cells. The agents are termed “recombinant immunotoxins,” and they kill cells by interfering with the cell’s ability to build proteins and grow, a mechanism not employed by other anti-cancer agents.   

Once Pastan and his lab partners had a drug in hand, they started clinical trials and awaited the results. Pastan said he would always remember the moment he got word of the trial’s effect on patients.   

“I was on vacation, and I got a call from my clinical colleague. ‘Ira! The leukemia counts have fallen by 50% and it’s only day one.’ The cancer went away entirely for many patients,” Pastan said. “Eight or 10 years later, some of those patients have survived without any detectable cancer. So, the drug can cure many people.”  

About 1,000 individuals in the U.S. are diagnosed with hairy cell leukemia each year. Up to 40% of patients who respond to chemotherapy will relapse within 10 years, which means there is a need for other therapies like the drug developed by Pastan. 

The immunotoxin approach is not Pastan’s only important scientific contribution. Over his 60-year career at NIH, he led a team that pioneered the field of receptor biology in animal cells. This has helped establish a framework that ultimately led to the use of targeted antibodies as a cancer therapy. 

These contributions to research “would be sufficient for anyone who wanted to be respected in the scientific community,” Misteli said. “He is a scientific Renaissance man. The impact that he has had over time has just been tremendous.” 

Pastan is also known for mentoring other scientists, including Nobel Prize winners Harold Varmus and Robert Lefkowitz as well as Doug Lowy, acting NCI director. 

“One of the major indicators of the influence that somebody has in science is if you look at the number of people that they produced and what they’re doing in the field,” said Glenn Merlino, scientific director for basic research at NIH’s Center for Cancer Research. 

“If you look at the number of people that have come out of his lab and where they are now, it’s ridiculous. There are Nobel Prize recipients, many people who became chairs of departments or in charge of an industry or are in leadership roles,” Merlino said. 

“These are extremely high-level people,” Misteli added. “When you talk to them, what’s impressive is that they don’t say, ‘oh, you know I went to Ira’s lab and I was lucky because it’s a great lab.’ Instead, they’ll tell you how he shaped their careers and how he really made a difference. He is an example of how a scientist should be and how you should think about science.”