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Rising Stars & Provocateurs

People who are accelerating our culture and advancing the conversation – for good or for ill. You may not have heard of them yet – but eventually everyone will.

Johanna in center in green sweater listening to students
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The lab is a battlefield

This time it’s personal 

Johanna Joyce, Cancer Warrior

Why you should care

Because the woman behind this cutting-edge cancer treatment is on a mission.

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Don’t let Johanna Joyce’s polite, soft-spoken demeanor fool you. The cancer biologist loves a good argument, a trait she credits to her Irish upbringing. “We [Irish] like to go against convention. If somebody says it’s so, we don’t automatically believe it,” she said. “I’ve always questioned anything anyone has told me.”

Joyce, 41, is bringing her hard-nosed Irish skepticism to the laboratory and challenging scientists to rethink how to fight cancer. Researchers have tried for decades to attack tumors by killing cancer cells, often to see them return after treatment. Joyce proposes targeting a more unlikely culprit — the white blood cells that surround and infiltrate tumors, known as macrophages. These cells roam every tissue of the body to engulf bacteria, dead cells and other waste. Many biologists dismissed macrophages as harmless “garbage trucks,” but Joyce didn’t think they were so innocent.

Many biologists dismissed macrophages as harmless “garbage trucks,” but Joyce didn’t think they were so innocent.

And she was right. In October, she broke news in the world-leading journal Nature Medicine that glioblastoma multiforme, the most common and deadliest form of brain cancer, can hijack macrophages in the brain and trick them into helping tumor cells proliferate rather than gobbling them up.

Defying dogma, she showed for the first time that an experimental drug that targets these macrophages might actually be able to control the disease by re-educating them to engulf tumor cells and could be used with existing therapies, such as radiation, to pack an even bigger punch. The results provide hope in the battle against a notoriously hard-to-treat cancer, which has an average survival time of only 15 months, even with chemotherapy and radiation. Joyce’s idea is currently being tested in early-stage clinical trials of glioblastoma patients and could be applied to other cancer types, including breast, ovarian, thyroid and pancreatic neuroendocrine cancer.

Green Blue and yellow micropscopic shapes.

Source: Pyonteck et al, Nature Medicine 2013

A glioblastoma tumor from a mouse treated with a CSF-1R inhibitor. The drug was shown to induce tumor-associated macrophages (green) to eat tumor cells (red).

Defying dogma, Joyce showed that an experimental drug that targets macrophages might actually be able to control the disease.

Since Joyce published her groundbreaking study, countless people have contacted her about enrolling in clinical trials — many of them young adults and parents of children with glioblastoma. “It’s very sobering to hear that people who are younger than me have been diagnosed,” she said. “It spurs you to push things as hard as you can.”

From an early age, Joyce has lived off the beaten path — literally. When she was 14, her parents moved Joyce and her four siblings from cosmopolitan London to the Irish countryside where they had grown up, so their kids could enjoy the same idyllic life. “There was always a very intense connection for them to Ireland and to the land,” said Joyce, who now lives with her husband, a neuroscientist, in New York City, five blocks from her lab at Memorial Sloan-Kettering Cancer Center.

Although Joyce initially hated leaving her friends behind, the Irish school system allowed her to explore a wider range of subjects than she could in the more structured English schools. She naturally gravitated toward science. “It’s what I always found most fascinating,” she said. “Part of me wants to always find new things and discover and walk into the unknown.”

After high school, Joyce headed to Trinity University in Dublin, where she became fascinated with genomic imprinting, a phenomenon in which the expression of certain genes depends on whether they were inherited from the individual’s mother or father, which can affect cancer risk. She then conducted her Ph.D. research on the subject at the University of Cambridge.

Johanna center, listening to Adam on left of page.

Student Adam Kaufman discusses his research project with Johanna Joyce.

At the time, scientists had begun exploring the possibility that tumors can trick neighboring noncancerous cells — the so-called tumor microenvironment — into producing proteins that help the tumor grow or spread. But many cancer researchers were skeptical. That was largely why Joyce joined Doug Hanahan’s lab at UC San Francisco, one of the few groups studying the tumor microenvironment at the time. 

Then tragedy hit. Joyce’s grandmother died of metastatic breast cancer in 2002, and her uncle died of glioblastoma two years later. Suddenly a vague desire to help others turned into a personal mission. When Joyce began her own lab at Sloan-Kettering in 2004, she focused much of her research on the diseases that had killed her own family members.

Recent clinical studies had reported higher levels of tumor-associated macrophages in more advanced glioblastoma. Why not use a drug that eradicated macrophages? Maybe it would prove even more effective than drugs that targeted tumor cells, since macrophages rarely change their gene expression. So Joyce treated glioblastoma-bearing mice with a drug that inhibited CSF-1R, a protein crucial for macrophage survival — and what she saw next shocked her. The drug stopped new tumors in their tracks and even shrank more advanced tumors. “The effects … were so dramatic,” she said. Even more surprising, the drug didn’t wipe out the macrophages. Instead, it had “re-educated” them to recognize and engulf tumor cells rather than help them grow, she reported in October.

The drug stopped new tumors in their tracks and even shrank more advanced  tumors. “The effects … were so dramatic,” she said.

Her findings are encouraging a paradigm shift in cancer research. “It’s a new way of thinking. Treatments that directly target the microenvironment are not something people have tried very much,” said Eric Holland, a researcher at the Fred Hutchinson Cancer Research Center in Seattle. “Johanna is certainly one of the main leaders in the field.”

Blue, green and some pinkish microscopic shapes.

A breast tumor treated with the chemotherapeutic drug paclitaxel. Macrophages (white) are recruited to produce cathepsin proteases (red) which block the death of tumor cells (blue and green).

That’s not to say microenvironment-directed therapy will be a silver bullet. More likely than not, these drugs will be used in combination with existing therapies, such as chemotherapy, radiation or drugs that directly target tumor cells. In fact, Joyce reported in 2011 that another experimental drug that acts on macrophages boosted the effectiveness of chemotherapy in mice with breast cancer. But critics point out that more human studies are needed to confirm that Joyce’s approach is effective. Tumors could still develop resistance, even to combined therapy, and administering different treatments at once may prove toxic to patients. In other words, there are still many unknowns. Nonetheless Joyce believes her approach “has a lot of potential.” 

Joyce knows the road from lab discovery to clinical therapy will be long and obstacle-filled. But the patients who contact her — especially young patients — are a reminder to keep going. “The goal is to really be doing the best research possible,” she said. “You really hope that you can make a discovery or multiple discoveries in your lifetime. But even if you make an impact on just one person, that was a life worth saving.”

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Meet The Author Melissa Pandika

Melissa Pandika is a lab rat-turned-journalist with eye to all things science, medicine and more. Like? Distance running, snails, late-night Korean BBQ + R&B slow jams.

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