Prostate Cancer Treatments Are Racing Ahead. Here’s a Big Reason Why.
Kira Peikoff was the editor-in-chief of Leaps.org from 2017 to 2021. As a journalist, her work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and two young sons. Follow her on Twitter @KiraPeikoff.
Dr. Stacy Loeb (left) and Dr. Heather Cheng were both recipients of a special early-career grant from the Prostate Cancer Foundation for young researchers.
In his lab at UCLA, Dr. Charles Sawyer discovered two drugs for metastatic prostate cancer that are now in routine use all over the world.
At the University of Washington at Seattle, Dr. Heather Cheng was part of a team that discovered the connection between BRCA2 mutations and advanced prostate cancer, and she recently opened a prostate cancer genetics clinic – a new frontier in the field.
At UT Southwestern Medical Center in Dallas, Dr. Nima Sharifi's pioneering research showed why certain drugs don't work in castrate-resistant prostate cancer, and now new therapies are being developed instead.
"We have good reason to believe that investing in young scientists is the way to go."
What Do These Researchers Share in Common?
They were all under 40 when they received a special grant for early-career scientists from the Prostate Cancer Foundation, the leading philanthropic organization that funds prostate cancer research. Experts say that the foundation's dedicated support for young innovators has been a game changer in contributing to the discovery of newer and better therapies for prostate cancer patients.
Howard Soule, the foundation's Executive Vice President and Chief Science Officer, was aware that many of the people who leave behind major legacies in science typically make their discoveries before age 40, like Albert Einstein, who was in his thirties when he published his paper on general relativity.
So back in 2007, the PCF decided to ramp up its support for young researchers.
"We have good reason to believe that investing in young scientists is the way to go, so we've created a program at PCF that is I believe is unique in the field," says Soule.
The Young Investigator Awards Program rigorously screens a pool of roughly 150 applicants for 20 to 25 awards that consist of funding for three years – and that's just the start.
"It's much more than sending them money," says Soule. "We celebrate them at annual meetings, we have a networking center with no equal in the field, and throughout the years of their three-year-award and basically forever, we create community. We are a safe place for them to land, they share data with us that's unpublished, and we provide a lot of feedback and stewardship to their donors."
Spotlighting Recipients: From the Study of Tumors to Twitter
Heather Cheng was in her thirties when she received her award three years ago. "It's been very, very helpful in allowing me to do the type of work I am really excited about doing," she says.
At the time, she had recently joined the faculty at the University of Washington after completing an MD/PhD medical scientist training program, internal medicine residency and hematology/oncology fellowship, and she was considering what new direction to take in her research. Several patients captured her imagination who were diagnosed at a very young age with metastatic prostate cancer, and "even though we had cool new drugs to extend life, these particular patients' cancers blew through everything."
"This is a new intersection because genetics has not been discussed in the context of care for men with prostate cancer that much."
She decided to make a niche out of understanding the connection between often early-onset aggressive prostate cancer and familial genetic risk, in order to improve treatment options for these patients. In 2016, Cheng launched a new clinic and invited any men to visit who have a family history of cancer and who are interested in genetic testing, or who have a known mutation and want to learn about treatment opportunities, or who want to know if their cancer tumor can be inherited.
"It's an open door to have a discussion because the technology and treatment potentials are so new," Cheng says. "There's a lot to learn."
It used to be that a doctor would ask a male patient about his family history, and if a mother had breast cancer at a young age, for example, and several other family members met the criteria for a genetic risk, then perhaps the patient had inherited a mutation in a cancer risk gene. But what to do next was unclear.
Now, doctors are taking men with a diagnosis of prostate cancer, sequencing their inherited DNA or their tumors, and finding out if they have mutations that could guide their treatment plan. For example, medications called PARP inhibitors have shown encouraging early results for men with a BRCA2 gene mutation and are now in clinical trials for treating prostate cancer.
"This is a new intersection because genetics has not been discussed in the context of care for men with prostate cancer that much," Cheng says. "This has changed practice because changes to national cancer guidelines have happened in less than five years. The change has happened so quickly that the field is not completely prepared for implementation and clinical logistics."
Another young investigator, New York University urologist and prostate cancer researcher Stacy Loeb, received her award at age 36 two years ago. She realized that no one had scientifically studied how patients are using crowdsourcing platforms like GoFundMe and YouCaring to raise money for their treatments. In her research, she found that there are many more campaigns for breast cancer and that they are more successful in crowdfunding than the prostate cancer campaigns.
"We have identified some gaps in advocacy and awareness for prostate cancer – fewer people know about it or discuss it, but it is a leading cause of death of U.S. men, so it is important to get more people aware," Loeb notes.
In fact, today the PCF releases data from a survey of more than 2,000 U.S. adults that reveals widespread ignorance about the disease. Two-thirds of respondents, for example, did not know that men with early stage prostate cancer experience no symptoms, and many were unaware that screening begins with a simple blood test.
Besides studying patient behavior, Loeb also wanted to better understand how physicians and scientists are using social media, and how their participation on platforms like Twitter could be fostered to promote greater dissemination of knowledge. So she helped start a monthly prostate cancer journal club on Twitter, hosted through the PCF science account. The club features an important new research paper in the field each month, and she invites the authors of the paper to participate in a 48-hour online discussion.
"The Journal Club is a monthly thing at most institutions," she says, "but typically it's one institution with people from one department. What's better about this is we have people who are doctors, nurses, scientists, patients, stakeholders participating from all over the world."
Why Do Young Innovators Have an Edge?
The environment matters, for one.
"We all bring different life experiences to the table, we grew up in different eras, so we have different norms and tools at our disposal that weren't available," says Loeb, who was one of the early adopters of social media in the urology space. She now gives a lecture at the annual PCF retreat on how to use social media to advance one's scientific career.
"The more you're invested into a system, the less you may be able to recognize its limitations."
But the advantage of youth is not just greater familiarity with the newest tools. It's also the existential benefit of not being entrenched in the way it's always been.
"Often there is a healthy skepticism of what's come before," explains Dr. Joseph La Brie, a clinical psychologist and professor at psychology at Loyola Marymount University. "That's connected to not being wedded to a programmatic view of the problem. There's a freshness and creative outlook because they are looking at it with a new set of eyes, and there's a desire to make their mark on the field, to be unique and innovative and not just follow in somebody else's footsteps."
And as Cheng puts it, "The more you're invested into a system, the less you may be able to recognize its limitations."
But it's notoriously difficult for scientists to get funding for innovative ideas without having already published preliminary data, which is what the National Institutes of Health and other funding bodies like to see. Eliminating that hurdle is a big part of why PCF's approach has been so effective, according to a veteran of the field, Johns Hopkins urologist Dr. Kenneth Pienta; his own groundbreaking research has been supported by PCF since he was a young scientist in the '90s.
"Any granting mechanism that allows people to fund ideas without a lot of preliminary data is a good thing," he declares.
Support for creative young minds is crucial across all endeavors, beyond any single disease or discipline. At a recent conference showcasing emerging technology for DARPA, the research arm of the Defense Department, expert panelists in artificial intelligence were asked: What is the single most important thing to focus on over the next decade?
Robotics pioneer Dr. Rodney Brooks may have put it best: "Figure out how to fund some really radical young mavericks and see what happens."
Kira Peikoff was the editor-in-chief of Leaps.org from 2017 to 2021. As a journalist, her work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and two young sons. Follow her on Twitter @KiraPeikoff.
How sharing, hearing, and remembering positive stories can help shape our brains for the better
Across cultures and through millennia, human beings have always told stories. Whether it’s a group of boy scouts around a campfire sharing ghost stories or the paleolithic Cro-Magnons etching pictures of bison on cave walls, researchers believe that storytelling has been universal to human beings since the development of language.
But storytelling was more than just a way for our ancestors to pass the time. Researchers believe that storytelling served an important evolutionary purpose, helping humans learn empathy, share important information (such as where predators were or what berries were safe to eat), as well as strengthen social bonds. Quite literally, storytelling has made it possible for the human race to survive.
Today, neuroscientists are discovering that storytelling is just as important now as it was millions of years ago. Particularly in sharing positive stories, humans can more easily form relational bonds, develop a more flexible perspective, and actually grow new brain circuitry that helps us survive. Here’s how.
How sharing stories positively impacts the brain
When human beings share stories, it increases the levels of certain neurochemicals in the brain, neuroscientists have found. In a 2021 study published in Proceedings of the National Academy of Sciences (PNAS), Swedish researchers found that simply hearing a story could make hospitalized children feel better, compared to other hospitalized children who played a riddle game for the same amount of time. In their research, children in the intensive care unit who heard stories for just 30 minutes had higher levels of oxytocin, a hormone that promotes positive feelings and is linked to relaxation, trust, social connectedness, and overall psychological stability. Furthermore, the same children showed lower levels of cortisol, a hormone associated with stress. Afterward, the group of children who heard stories tended to describe their hospital experiences more positively, and even reported lower levels of pain.
Annie Brewster, MD, knows the positive effect of storytelling from personal experience. An assistant professor at Harvard Medical School and the author of The Healing Power of Storytelling: Using Personal Narrative to Navigate Illness, Trauma, and Loss, Brewster started sharing her personal experience with chronic illness after being diagnosed with multiple sclerosis in 2001. In doing so, Brewster says it has enabled her to accept her diagnosis and integrate it into her identity. Brewster believes so much in the power of hearing and sharing stories that in 2013 she founded Health Story Collaborative, a forum for others to share their mental and physical health challenges.“I wanted to hear stories of people who had found ways to move forward in positive ways, in spite of health challenges,” Brewster said. In doing so, Brewster believes people with chronic conditions can “move closer to self-acceptance and self-love.”
While hearing and sharing positive stories has been shown to increase oxytocin and other “feel good” chemicals, simply remembering a positive story has an effect on our brains as well. Mark Hoelterhoff, PhD, a lecturer in clinical psychology at the University of Edinburgh, recalling and “savoring” a positive story, thought, or feedback “begins to create new brain circuitry—a new neural network that’s geared toward looking for the positive,” he says. Over time, other research shows, savoring positive stories or thoughts can literally change the shape of your brain, hard-wiring someone to see things in a more positive light.How stories can change your behavior
In 2009, Paul Zak, PhD, a neuroscientist and professor at Claremont Graduate University, set out to measure how storytelling can actually change human behavior for the better. In his study, Zak wanted to measure the behavioral effects of oxytocin, and did this by showing test subjects two short video clips designed to elicit an emotional response.
In the first video they showed the study participants, a father spoke to the camera about his two-year-old son, Ben, who had been diagnosed with terminal brain cancer. The father told the audience that he struggled to connect with and enjoy Ben, as Ben had only a few months left to live. In the end, the father finds the strength to stay emotionally connected to his son until he dies.
The second video clip, however, was much less emotional. In that clip, the same father and son are shown spending the day at the zoo. Ben is only suggested to have cancer (he is bald from chemotherapy and referred to as a ‘miracle’, but the cancer isn’t mentioned directly). The second story lacked the dramatic narrative arc of the first video.
Zak’s team took blood before and after the participants watched one of the two videos and found that the first story increased the viewers’ cortisol and oxytocin, suggesting that they felt distress over the boy’s diagnosis and empathy toward the boy and his father. The second narrative, however, didn’t increase oxytocin or cortisol at all.
But Zak took the experiment a step further. After the movie clips, his team gave the study participants a chance to share money with a stranger in the lab. The participants who had an increase in cortisol and oxytocin were more likely to donate money generously. The participants who had increased cortisol and oxytocin were also more likely to donate money to a charity that works with children who are ill. Zak also found that the amount of oxytocin that was released was correlated with how much money people felt comfortable giving—in other words, the more oxytocin that was released, the more generous they felt, and the more money they donated.
How storytelling strengthens our bond with others
Sharing, hearing, and remembering stories can be a powerful tool for social change–not only in the way it changes our brain and our behavior, but also because it can positively affect our relationships with other people
Emotional stimulation from telling stories, writes Zak, is the foundation for empathy, and empathy strengthens our relationships with other people. “By knowing someone’s story—where they come from, what they do, and who you might know in common—relationships with strangers are formed.”
But why are these relationships important for humanity? Because human beings can use storytelling to build empathy and form relationships, it enables them to “engage in the kinds of large-scale cooperation that builds massive bridges and sends humans into space,” says Zak.
Storytelling, Zak found, and the oxytocin release that follows, also makes people more sensitive to social cues. This sensitivity not only motivates us to form relationships, but also to engage with other people and offer help, particularly if the other person seems to need help.
But as Zak found in his experiments, the type of storytelling matters when it comes to affecting relationships. Where Zak found that storytelling with a dramatic arc helps release oxytocin and cortisol, enabling people to feel more empathic and generous, other researchers have found that sharing happy stories allows for greater closeness between individuals and speakers. A group of Chinese researchers found that, compared to emotionally-neutral stories, happy stories were more “emotionally contagious.” Test subjects who heard happy stories had greater activation in certain areas of their brains, experienced more significant, positive changes in their mood, and felt a greater sense of closeness between themselves and the speaker.
“This finding suggests that when individuals are happy, they become less self-focused and then feel more intimate with others,” the authors of the study wrote. “Therefore, sharing happiness could strengthen interpersonal bonding.” The researchers went on to say that this could lead to developing better social networks, receiving more social support, and leading more successful social lives.
Since the start of the COVID pandemic, social isolation, loneliness, and resulting mental health issues have only gotten worse. In light of this, it’s safe to say that hearing, sharing, and remembering stories isn’t just something we can do for entertainment. Storytelling has always been central to the human experience, and now more than ever it’s become something crucial for our survival.
Want to know how you can reap the benefits of hearing happy stories? Keep an eye out for Upworthy’s first book, GOOD PEOPLE: Stories from the Best of Humanity, published by National Geographic/Disney, available on September 3, 2024. GOOD PEOPLE is a much-needed trove of life-affirming stories told straight from the heart. Handpicked from Upworthy’s community, these 101 stories speak to the breadth, depth, and beauty of the human experience, reminding us we have a lot more in common than we realize.
A new type of cancer therapy is shrinking deadly brain tumors with just one treatment
MRI scans after a new kind of immunotherapy for brain cancer show remarkable progress in one patient just days after the first treatment.
Few cancers are deadlier than glioblastomas—aggressive and lethal tumors that originate in the brain or spinal cord. Five years after diagnosis, less than five percent of glioblastoma patients are still alive—and more often, glioblastoma patients live just 14 months on average after receiving a diagnosis.
But an ongoing clinical trial at Mass General Cancer Center is giving new hope to glioblastoma patients and their families. The trial, called INCIPIENT, is meant to evaluate the effects of a special type of immune cell, called CAR-T cells, on patients with recurrent glioblastoma.
How CAR-T cell therapy works
CAR-T cell therapy is a type of cancer treatment called immunotherapy, where doctors modify a patient’s own immune system specifically to find and destroy cancer cells. In CAR-T cell therapy, doctors extract the patient’s T-cells, which are immune system cells that help fight off disease—particularly cancer. These T-cells are harvested from the patient and then genetically modified in a lab to produce proteins on their surface called chimeric antigen receptors (thus becoming CAR-T cells), which makes them able to bind to a specific protein on the patient’s cancer cells. Once modified, these CAR-T cells are grown in the lab for several weeks so that they can multiply into an army of millions. When enough cells have been grown, these super-charged T-cells are infused back into the patient where they can then seek out cancer cells, bind to them, and destroy them. CAR-T cell therapies have been approved by the US Food and Drug Administration (FDA) to treat certain types of lymphomas and leukemias, as well as multiple myeloma, but haven’t been approved to treat glioblastomas—yet.
CAR-T cell therapies don’t always work against solid tumors, such as glioblastomas. Because solid tumors contain different kinds of cancer cells, some cells can evade the immune system’s detection even after CAR-T cell therapy, according to a press release from Massachusetts General Hospital. For the INCIPIENT trial, researchers modified the CAR-T cells even further in hopes of making them more effective against solid tumors. These second-generation CAR-T cells (called CARv3-TEAM-E T cells) contain special antibodies that attack EFGR, a protein expressed in the majority of glioblastoma tumors. Unlike other CAR-T cell therapies, these particular CAR-T cells were designed to be directly injected into the patient’s brain.
The INCIPIENT trial results
The INCIPIENT trial involved three patients who were enrolled in the study between March and July 2023. All three patients—a 72-year-old man, a 74-year-old man, and a 57-year-old woman—were treated with chemo and radiation and enrolled in the trial with CAR-T cells after their glioblastoma tumors came back.
The results, which were published earlier this year in the New England Journal of Medicine (NEJM), were called “rapid” and “dramatic” by doctors involved in the trial. After just a single infusion of the CAR-T cells, each patient experienced a significant reduction in their tumor sizes. Just two days after receiving the infusion, the glioblastoma tumor of the 72-year-old man decreased by nearly twenty percent. Just two months later the tumor had shrunk by an astonishing 60 percent, and the change was maintained for more than six months. The most dramatic result was in the 57-year-old female patient, whose tumor shrank nearly completely after just one infusion of the CAR-T cells.
The results of the INCIPIENT trial were unexpected and astonishing—but unfortunately, they were also temporary. For all three patients, the tumors eventually began to grow back regardless of the CAR-T cell infusions. According to the press release from MGH, the medical team is now considering treating each patient with multiple infusions or prefacing each treatment with chemotherapy to prolong the response.
While there is still “more to do,” says co-author of the study neuro-oncologist Dr. Elizabeth Gerstner, the results are still promising. If nothing else, these second-generation CAR-T cell infusions may someday be able to give patients more time than traditional treatments would allow.
“These results are exciting but they are also just the beginning,” says Dr. Marcela Maus, a doctor and professor of medicine at Mass General who was involved in the clinical trial. “They tell us that we are on the right track in pursuing a therapy that has the potential to change the outlook for this intractable disease.”