SAN DIEGO – With two decades of cancer research under his belt, Tom is no stranger Marsilje to project deadlines. However, it has never faced anyone like this before.
He is in a race against the clock in an unlikely to cure his own incurable colon cancer before he leaves his wife and two little girls search.
Marsilje, 44, knows that if he does nothing, that is keeping tumors at bay with chemotherapy eventually explode in growth mode. It’s a matter of when, not if.
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So he is doing everything possible to outsmart your cancer before it’s too late. He enlisted the help of a small team of scientists who think they might have identified a new approach to revving up your immune system. If it works, it could open new avenues for other patients with difficult cancers to treat.
has not been easy. Two of the most commonly used therapies for cancer have stopped working. A health condition unrelated tempting him out from the clinical trials. Your search for their own genetic information recently left him with a (very important) pulmonary atelectasis.
And it is still not sure his team of advisors will be able to convert their research into an experimental therapy for Marsilje -. Or they’ll work
Researchers and doctors who spend their days battling cancer point Marsilje history as a model for other patients. Everyone, they say, must learn to take command of their own care and insist that everyone who receives a possible decision to stay alive.
But if his story is an inspiration, it is also a warning.
Marsilje (pronounced mar-SIL-ya) is a medical chemist who knows how to decipher their own genetic data, how to read the scientific literature, and who to ask for help. Even you live in the right place :. San Diego, where biotechnology companies and medical research institutions are almost as common as sea and taco
“I am the empowered patient can probably” Marsilje said.
Yet even he has faced enormous challenges familiar to many patients: It is difficult to enter the most promising clinical trials, and not many of them to certain cancers. The mere fact of a tumor sample may be a search for his own. And while new discoveries raise the emotion, it is a long way between the time “aha!” In the laboratory and actual treatment.
Sometimes it seemed as if Marsilje had hit the end of the road – only to have his hopes revived thanks to chance encounters with prominent scientists. That’s part of its history, also :. It is clear how important it is pure luck can be when you’re fighting steep odds
A man of gentle and quiet voice that can spend hours analyzing data, Marsilje now has a clear glimmer of hope: Plans are underway for a clinical trial at the University of California, San Diego, Cancer Center in which he is already receiving treatment. He and his team hope to be able to join.
If accepted, you will receive a personalized vaccine scheduled to stimulate their immune system cells to attack the most vulnerable mutations their tumors. If it worked, you could turn your cancer into a manageable chronic illness or, in the best case, even melt away.
The approach is called a vaccine because neoantigen prompts the immune system to home in on warning signs, known as neo-antigens, planted on the surface of malignant cells. It is part of the new hot wave of immunotherapies that have generated considerable enthusiasm -. Although they have helped only a fraction of patients with cancer
Experts see real promise in personalized vaccines neoantigen, but warn it could take years to see the benefits. And that the promise could still weaken after the last analysis. There are a lot of reasons, after all, why there is not any therapies on the market.
Marsilje is clear about the long odds facing eyes. But it is also unabashedly optimistic.
“I set my hopes on a percent probability of 10 or 20,” he said, “because that is certainly better than zero.”
waiting for cancer
Marsilje had hoped to have cancer at some point in their lives. He just did not expect it would be so soon.
Growing up, he was already “abnormal serious” about pursuing the discovery of cancer drugs, since he had seen many members of the affected family. His photographic memory and fascination with science helped him push through his scientific training.
Then, when he was 27 years old and Marsilje finishing his doctorate in medicinal chemistry from the State University of New York at Buffalo, his mother he was diagnosed with advanced pancreatic cancer at age 54 he and his sister cared for her in the last months of his life. It emerged increasingly determined to use science to fight cancer.
Marsilje built a busy and fulfilling lives in San Diego, where he has worked for the division of corporate research at Novartis since 2003. He married a woman who is so technically good as he is – an electrical engineer. Towards the end of 30 years, who had a toddler and a baby and spent as much time as they could in the redwood forests in northern California.
Because of their family history of cancer, Marsilje had planned to start getting colonoscopies after age 40.
Then, at age 39, he began to have some gastrointestinal problems. For a time he had thought it might be intolerant to gluten. He wondered if he had a parasite. Finally, he scheduled a colonoscopy .
The morning of her appointment, Marsilje scored a great professional victory when an experimental cancer drug that had been synthesized for the first time had its moment of rupture at a scientific meeting. The results of the first human trials were promising :. The drug (now sold as Zykadia) seemed to work
it seemed finally had helped achieve a blow against cancer.
Still “walking on air” Six hours later, Marsilje entered his test. He woke up when he heard the doctor tell his wife: Your husband has colon cancer. We have to schedule surgery immediately.
Surgery and chemotherapy was given months of remission and hope that he had dodged a bullet. He began to run regularly.
But more than a year after he was first diagnosed, devastating news: The cancer had spread to his lungs and distant lymph nodes. It would be too dangerous to operate. And the surgery could not catch any cancer cells anyway.
His illness was incurable.
diagnostic lights a fire
The day Marsilje got the first indications that his cancer had spread, put on running shoes and succeeded, for the first time to run a half marathon without stopping to rest.
And he really has to work.
Marsilje As a friend and former colleague Eric Murphy put it: “Take that unconditional researcher and light a fire under him, and that’s what happened here.”
He was a vegetarian. He started running six miles every other day. He read everything he could find relevant scientific literature. He spattered her oncologist with questions. Be emailed many cancer researchers had known in recent years, asking what they had been hearing about colon cancer.
And he began to investigate the clinical trials, so the flowcharts in Excel format with which wanted to try first, and where he would go after each therapy if not later.
“I set my hopes on one occasion 10 or 20 percent, because that is certainly better than zero.”
hours on the job, working on his laptop at home or while eating a salad at your desk for long lunches at work, where their heads recommends spend time focusing on their own health.
Started by dragging clinicaltrials.gov, the database of clinical trials it is very difficult to navigate, “even for a scientist,” he said. Marsilje came up with an initial list of dozens of trials, and then cut down, focusing on immunotherapies that seemed more aggressive.
“When the game clock ticking, and behind, bring it to the big fish,” he said.
Soon he and his oncologist found what looked like the judgment perfect Immunotherapy: It was at his home in San Diego, and the experimental treatment would be used on top of, rather than instead of it already on the market
But at a meeting to sign the papers, it came up with an improvised so that Marsilje had a small melanoma, unrelated to your colon cancer, removed a few weeks earlier. The paperwork was taken out of the hands; He not allowed to join this lawsuit or others with the same restriction. (Patients with secondary cancers are often excluded from the trials of three to five years, for fear that their secondary cancer could confuse the test results.)
Marsilje was out of options.
Last Fight “chemo brain ‘
He was not out of time, however.
has joined the many patients with incurable cancer who undergo chemotherapy or taking drugs aimed at prolonging life. Many with cancer are living for several years in these regimes, and a small fraction can live more than five years.
This strategy is still working to Marsilje. He did six months in a targeted therapy, and once their tumors began to grow, changed to a combination of chemotherapy and a different targeted therapy that has been keeping the cancer under control for almost a year.
However, chemotherapy has been difficult: family trips to redwoods are not practical anymore. That usually can not run long distances. He tires easily. And he suffers what is known as “chemo brain.” Having no recollection of an email sent or forget where to go on your daily commute is a setting dial for a man who can usually remember information in an instant. However, chemotherapy does not appear to interfere with their ability to speak or remember scientific concepts.
Marsilje has never stopped working full time for Novartis, although no longer working in the laboratory. He moved to a consulting role for oncology projects.
has also become a vocal leader in the community of patients with colon cancer. He is well aware of the advantages in navigating treatment options, and try to return the favor. As an advocate, he has given speeches and pressed lawmakers to increase funding for research and make it easier to get colonoscopies. As a blogger, which translates into plain English results of clinical trials and advises other patients on how to advocate for themselves.
His tone is optimistic – underlined by the title of his blog “Adventures in Living Terminal optimistic” – in which includes photos of himself running or jumping in the pool, with the hashtag ” #CannonballLife. “
To Marsilje, there is something surreal about tumors within it are lurking in wait. Since getting its initial colon surgery more than four years ago, which has had no symptoms of the disease. His disease is only seen on a CT scan.
“I joke that I’m a perfect type health,” he says, “except for one small problem.”
A stroke of luck
proved to be a series of lucky breaks that put Marsilje seeking to cure your cancer back on track.
A few weeks after being excluded from the San Diego, Marsilje was in the audience at a panel discussion about cancer when his ears perked: A biologist prominent cancer was talking about helping a patient to get your tumors sequenced so that doctors could understand genetic peculiarities of their cancer -. and potential weaknesses
On his way home that night, Marsilje could not stop thinking about the talk. The cold emailed biologist, Geoffrey Wahl at the Salk Institute for Biological Studies, and asked for help.
To his surprise, Wahl responded immediately. They met for lunch the next day, in a cafe overlooking the Pacific Ocean. Wahl promised to try to find a way to help get your cancer Marsilje sequenced, too.
Recalling that the promise of today, Wahl uses the Yiddish word bashert : It was meant to be
“When game time runs, and behind, the big fish is taken.”
Later that night, the woman Wahl needed to replace her at a dinner attended by leading scientists and philanthropists who are preparing for a charity bike ride. Wahl happened to be sitting next to Craig Venter pioneering geneticist and entrepreneur who now runs a biotech company in San Diego that is building world’s largest operation dedicated to the sequencing of the human genome.
Wahl Venter barely knew, but he looked directly into my eyes and made the call 😕 What good is a bike ride charity if you can not help someone like Marsilje
“I just said, ‘Absolutely, you get more and get the tumor sample for us,'” recalled Venter respond. His company paid for Marsilje to get both her cancer and blood sequenced. In return, the company Venter, human longevity, it must maintain genetic data Marsilje for future research.
Now Marsilje had their genetic information, but he still did not have a way to do anything with it – until he met two part-time researchers affiliated with human longevity :. Stephen Schoenberger and immunologist Dr. Ezra Cohen UCSD oncologist
In his other works, they were working on neoantigens, focusing on cancers like yours, who have barely benefited from the new wave of immunotherapies. Your project might be able to help, they told Marsilje. At least, it would be scientifically interesting.
would want to join?
A shot in the pot
So far, the power of immunotherapy seems have much to do with number significant genetic errors in cancer that is trying to assume. Most mutations have a tumor, more red flags go up as neoantigens that immune cells can recognize and attack patient.
“The feeling in the field now is that it is a numbers game,” Schoenberger said. “Each mutation is thought to be a ticket for the lottery. More tickets, more chances for a victory.”
Former President Jimmy Carter whose famous cancer reached remission with the immunotherapy drug Keytruda even after it had spread to the brain, had plenty lottery tickets :. of he had melanoma, the type of cancer most mutations
The type of colon cancer has Marsilje, however, has relatively few mutations -. Suggesting their immune system probably would not have much of a shot
“People have been put off by the idea of having very few lottery tickets,” Schoenberger said. He thinks it should not be.
researchers working in cancer immunotherapy with many mutations, such as melanomas, typically use computer algorithms to predict which of these mutations could make juicy targets for the immune system. Schoenberger and his team worried that such an approach would not work for certain types of cancer with few mutations, such as type of colon cancer Marsilje. But they found a solution: Because there were so few mutations, which could test them all individually old-fashioned, in the wet lab
So that’s what they did. Schoenberger in the laboratory at the La Jolla Institute for Allergy and Immunology, analyzed the genetic data of Marsilje to get to a short list – 32 tumor mutations – which are believed to be the most promising targets. a lot of small fragments were synthesized proteins, called peptides, so that each includes a single mutation for Marsilje data. peptides are then exposed to the blood of Marsilje, and measure what happened.
Immune cells in the blood attacked about a dozen of the peptides. That’s more than computer algorithms would have predicted. It was a sign that cancer cells may not need a large number of mutations for the immune system to recognize as dangerous -. Which it means Marsilje tumors could be vulnerable to attack, too, if only your immune system could simply get a boost
That’s where a personalized vaccine neoantigen come.
of Marsilje, Dr. Tony Reid of UCSD, said that science is not at a level where it is possible to predict the chances of a therapy of this kind of work for a given patient. But he and the rest of the team thinks that the signal is strong enough to justify serious consideration the approach Marsilje.
“are confident that what we are seeing is real and potential clinical value for Tom,” Schoenberger said.
Pending the opportunity to be a guinea pig
The next big step :. Marsilje get enrolled in a clinical trial in which laboratory work could become a therapy
The wheels are in motion to human longevity to sponsor a clinical trial in which each enrolled patient get a personalized vaccine. If Marsilje can not enter into that trial, or if not come to fruition fast enough, the team will look elsewhere. Marsilje still checks the registry federal trial every Monday to update their spreadsheets with backup options.
Marsilje want to try something as soon as possible. At a recent meeting with his team, someone suggested to wait until their tumors have grown enough so that researchers could easily get another sample as another way to confirm their work.
Marsilje intervened immediately.
“My concern is waiting too long,” he said. “I do not know if [chemotherapy] will work another three years or three months. I do not know what it will be.”
Marsilje is convinced that his quest to fight his cancer does not get in the way of passing time with his family. (Is granted only he did not have the time to see comedies.)
Helps hardly sleeps: He is on his laptop working on his own project or trying to help other patients every night for a few hours after putting her children to bed, and then rises before the sun for a few more hours of work before they wake up.
His greatest driving force to live: wanting to be there for their daughters when needed. The first received her diagnosis of incurable cancer, the idea lingered jet off to see the world with his family when he still could, but chose not to. It is less concerned about the milestones that small moments of everyday life.
recently she taught her daughter 5 years old, Eleni, to play football.
And with his 9-year-old daughter, Amelie, played a lot of Minecraft. It is difficult for her to see how fatigued by chemotherapy, explaining to her as his “sleep medicine.”
For Amelie, summarizing his quest to design your own cure this way: “. We are trying to find a drug that can take on will not have to take medication to sleep more”