Watching his brother slowly die was enough to convince Filko Prugo he didn't want to go the same way. He was willing to do whatever he could to ensure his three children would avoid that fate, too.
So, among other things, the New York City resident volunteered for a research trial, testing an experimental vaccine for people like him, who carry an extra genetic risk for certain cancers.
If all goes as hoped, the vaccine, which he received four times, will keep him from developing prostate, breast or pancreatic cancer.
As a trial participant, he's also being monitored carefully for the two years of the trial, so any tumors that do develop will be caught early when they are likely to be the most survivable.
If the vaccine works and doesn't cause other safety problems ‒ and so far, it hasn't ‒ it will be tested in more people and over longer periods. In the meantime, vaccines that help prevent cancer recurrences are progressing with an advance in melanoma vaccines announced on Monday.
Long-term, the vision is to prevent nearly all cancers, a Holy Grail that researcher Dr. Susan Domchek and others have been working toward for decades. She says it will likely take decades more to achieve fully.
"I believe in what we're doing, but I also recognize what's needed to get from A to Z," said Domchek, a breast cancer specialist at Penn Medicine in Philadelphia.
She says the project is about at letter K right now ‒ nearly midway through the development process. "What can be frustrating to patients is: Science takes time."
Different types of cancer vaccines
Cancer vaccines have been a dream for nearly as long as there have been vaccines.
The only ones readily available today are those that block cancer-causing viruses. For example, the HPV vaccine against human papillomavirus, given to children starting at 9, is extremely effective at preventing cervical cancer, some head and neck and other cancers in men.
A different type of cancer vaccine is being tested in patients who already have cancer ‒ though it's still probably a handful of years away from the first federal approvals.
A key reason mRNA vaccines were ready to go so quickly against COVID-19 was that they were already being developed against cancer. By then, researchers had realized the most effective near-term use of a vaccine was probably to stop cancer from recurring, rather than to prevent it from happening at all.
They also realized after years of failures that vaccines alone weren't enough to block a recurrence. But by pairing a vaccine with other treatments, they could make a profound difference in a patient's care.
On Monday, as part of the annual American Society of Clinical Oncology conference in Chicago, Merck and Moderna released information about a cancer vaccine they are jointly developing.
The new data in patients with advanced melanoma, a type of skin cancer, shows that three years after receiving a vaccine, along with taking a Merck immunotherapy called Keytruda, 89% of patients remain free of metastatic growth. Of patients who receive Keytruda alone, 68% remain free of metastases at three years, showing the vaccine provides substantial benefit.
"This is the promise," said Dr. Marjorie Green, senior vice president of oncology global clinical development with Merck.
The great challenge with these vaccines to prevent recurrences is that ‒ at least for now ‒ they must be personalized. Each vaccine has to be tailored to each person's tumor.
Because cancer cells are a person's own cells that have figured out how to grow and divide undetected, they are difficult for the immune system to recognize as "foreign" and root out.
But also, because they divide so often they typically have changes that are not present in normal cells. It's these changes, so-called neoantigens on the surface of the cells that can act as flags to identify cancer cells, Green explained. Cancer vaccines are designed to get the immune system to recognize the neoantigens present within a person's own tumor cells and attack them.
The combination of the vaccine, along with Keytruda fires up the immune system and enables it to wipe out tumor cells throughout the body, she said.
The two companies are launching a larger trial of the same approach in melanoma and are also testing the same approach in non-small-cell lung cancer.
Others are testing a similar type of vaccine in head and neck cancers and colon cancer, though all these vaccines are expected to be years away from approval.
"This is such a fun time to be an oncologist," Green said. "If you have to have this horrible diagnosis, we're so much in a better place now than we were 20 years ago."
So close, but not close enough for everyone
Even with this type of cancer vaccine, though, challenges remain.
Dr. Corey Casper, a cancer and infectious disease expert in Seattle, said he worries that rare and pediatric cancers are being left behind by large commercial efforts like Merck's and Moderna's.
Of the 200 cancer drugs approved over the past few years, only three or four were for pediatric cancers, said Casper, who is also president and CEO of Access to Advanced Health Institute, a nonprofit biotech firm in Seattle. He wants the federal government to support cancer vaccine development for children and young people with cancer, so they'll be able to benefit from the advances, too.
"I think the kids need a hand. Parents need a hand," he said. "If the government helps de-risk that, in pediatric cancers, we'll make rapid leaps and bounds."
He's haunted, he said, by a patient recently referred to him, a 21-year-old woman named Zoe who has already been coping with aggressive ovarian cancer for three years.
She wasn't eligible for clinical trials for immunotherapy, so she's now "battling cancer in the final stages of her life," Casper said. "We know the technology can be there, but we just can't avail it to every patient who needs it. That breaks my heart."
One hope, he said, is that researchers will be able to identify a limited number of neoantigens that are most likely to be present in most cancers and create a ready-made "library" of these.
Then, once a patient's tumor is analyzed, a personalized selection can be made from this library and the vaccine cam be mixed practically at their bedside and rapidly delivered.
The personalization makes a lot of sense, said Dr. Catherine Wu, a medical oncologist at the Dana-Farber Cancer Center in Boston. Cancer cells have lots of unique mutations and a personalized vaccine can help target each cancer's distinctive features.
Personalization also makes sense, she said, because it means "you get another shot" if the cancer evolves and needs a modified treatment.
The involvement of big companies like Merck and Moderna in cancer vaccines makes Wu optimistic that they will figure out a way to make these treatments feasible and more affordable over time. The cost of preventing cancer from recurring should offset the cost of these vaccines, Wu said.
Many questions remain unanswered about these types of vaccines, though, like what are the best neoantigens to target; how to trigger the right amount of immune reaction, but not too much; and whether to use mRNA technology, an older vaccine technology or both, said Robert Schreiber, a tumor immunologist and director of the Washington University School of Medicine Bursky Center for Human Immunology and Immunotherapy in St. Louis.
Still, "if I'm a patient and I've failed all other kinds of therapies and someone offers me a personalized therapy, I'm going to go for it," Schreiber said.
Decades to prevent cancer from gaining a foothold
Olivera Finn has been working for four decades on a vaccine to stop cancer from ever taking hold.
Finn, an immunologist at the University of Pittsburgh, has been focused on a specific molecule that occurs in more than 80% of solid tumors, called MUC1.
She's currently testing a vaccine in people who have high-risk polyps removed during colonoscopies. By vaccinating them after the polyp has been removed and following them, she hopes to prevent them from developing colon cancer. "If you show immunity, safety and efficacy in this setting, the same can be expected in other precancer settings," she said.
She's also trying the same approach in women diagnosed with ductal carcinoma in situ, or DCIS, a precancerous condition that puts them at high risk for breast cancer. Eventually, she hopes her approach will enable them to avoid surgery.
In the trials, she gives two shots two weeks apart to prime the immune system, a third two months later to boost it, plus a fourth at a year. She's not sure yet whether people will need another booster at 10 years or another time interval.
But if tumor cells start to grow later, Finn said, those cells should actually act as their own booster.
Dr. Elizabeth Jaffee, a medical oncologist and immunologist at Johns Hopkins University in Baltimore, takes a similar approach against a different mutation.
The KRAS gene is typically the first to mutate in the cascade of genetic changes to cause many different types of solid tumors. Pancreatic cancer, Jaffee's specialty, would not happen for instance, if the KRAS gene didn't mutate.
She's currently testing a KRAS-targeted vaccine in people at high risk for pancreatic cancer. Her first patients were vaccinated about a year ago and are still making an immune response, suggesting their bodies would still fight off cancer cells, she said.
Finn has shown that a vaccine approach may not work to prevent lung cancers in heavy smokers because of the damage to the immune system. It must either catch them earlier in their smoking history or something else needs to be used to prevent cancer in those individuals, she said.
And even the best cancer vaccine won't stop every cancer, just as the flu vaccine doesn't stop every infection, Finn said. But ideally, it will reduce the risk and "keep it at bay as long as possible."
Changing the path of disease, one person at a time
Prugo, the New Yorker who has been in a vaccine trial, knows it's going to be a very long time before a vaccine will be able to prevent nearly all tumors or even those caused by inherited mutations like his own.
But he says it'll never happen if people like him don't volunteer for research trials.
"Getting involved in clinical trials is of the utmost importance if we want to change the trajectory of difficult-to-treat diseases," he said.
Prugo carries the BRCA2 (for BReast CAncer gene 2) mutation, which increases the risk for several cancers, including breast cancer. Typical men have less than a 0.1% chance of developing breast cancer over their lifetime, but men with the BRCA2 mutation have as much as a 10% chance ‒ 100 times higher risk.
After watching his brother die of breast cancer, Prugo had surgery to remove his breast tissue, dramatically reducing the risk. "As a male, there's just less associated with male breasts," he said. "Honestly, it was an easy decision."
His father had already died of cancer, likely not connected to BRCA2, but an uncle who died of cancer years ago may have had a BRCA2-related disease, he said.
After watching so many people close to him endure ultimately futile treatment, Prugo gave up a lucrative career as a lawyer working with the biotechnology industry.
In his late 40s, he began studying for a doctorate at Columbia University, researching how the BRCA2 mutation leads to pancreatic cancer in mice.
His salary is a fraction of what it once was. But he says it doesn't matter.
"When you see your dad die of cancer and the suffering I saw my brother go through ‒ it was horrific," he said. Plus, he knew his future would likely be the same. "When you stare that reality in the face, you realize how unimportant money is."
What matters more, he said, is what he's doing to help others with cancer now or who might develop it in the future.
"This way, I can always look back and say I tried. I tried for myself and I tried for my kids," Prugo said. "What else can we do in life?"
Karen Weintraub can be reached at kweintraub@usatoday.com.
