Vitals
Current affiliation: German Cancer Research Center
Age: 37
PhD alma mater: Ruprecht Karl University of Heidelberg
My role model is: “Marie Curie, because she dedicated her life to studying the most remarkable natural phenomenon, radioactivity, while collaborating closely with her husband, just as I do in my work.”
When I’m not doing chemistry, I enjoy: “Driving powerful cars, exploring mines, and attending hard and heavy concerts.”
Nov. 27, 2012, was a fateful day for Martina Benešová-Schäfer. Not only did she begin work on a PhD project that would eventually lead to a blockbuster drug, she also met Martin Schäfer, a researcher in her group whom she would marry 10 years later.
The drug that emerged from her PhD work at the German Cancer Research Center (DKFZ) is a prostate-cancer treatment called Pluvicto. It contains lutetium-177, a radionuclide that emits β particles to kill cancer cells. This radioactive cargo is carried by a three-part molecule: a metal-binding chelator compound that holds lutetium; a targeting molecule that sticks to the cells’ prostate-specific membrane antigen (PSMA) receptors; and a linker that connects the two.
Pluvicto won regulatory approval from the US Food and Drug Administration in 2022 and last year racked up almost $2 billion in sales for Novartis. Today, Benešová-Schäfer leads her own research group at the DKFZ and is developing new ways to treat cancer with targeted radiation.
“She was a top talent,” recalls Klaus Kopka, who led the DKFZ’s radiopharmaceutical chemistry division during Benešová-Schäfer’s PhD. Kopka is now director of the Institute of Radiopharmaceutical Cancer Research at the Helmholtz-Zentrum Dresden-Rossendorf and collaborates with Benešová-Schäfer’s group. “She’s really open minded about working in a multidisciplinary field, not only with chemists but biologists, engineers, medical physicists, physicians, and clinical scientists.”
Benešová-Schäfer was first introduced to radioactivity during her childhood in the Czech Republic, when her father, a geologist and mineralogist, explained the concept to her. “It totally fascinated me,” she says. “I immediately knew I wanted to work with radioactivity when I was an adult.”
When she arrived at the DKFZ, researchers there had already developed an imaging agent called PSMA-11, which carries positron-emitting gallium-68 to prostate cancer cells for positron emission tomography (PET) diagnostic scans. “My PhD project was to adjust PSMA-11 so it could be used for therapy,” Benešová-Schäfer says.
The compound’s targeting unit, glutamate-urea-lysine, remained the same. But the researchers wanted to swap the gallium radionuclide with lutetium-177, which had already shown clinical promise as a cancer treatment. Lutetium had to be tethered to the molecule in a different way than gallium, using a chelator called DOTA, but DOTA seemed to hamper PSMA-11’s targeting ability.
To fix the problem, Benešová-Schäfer made variants of the peptide-based linker section and tested the compounds in mice. She eventually found a linker with a naphthyl group that strengthened binding to the PSMA receptor. The finished compound, Lu-177–PSMA-617, was subsequently licensed, taken through clinical trials, and approved as Pluvicto.
As the drug progressed through clinical trials, Benešová-Schäfer moved on to postdoctoral studies at the Paul Scherrer Institute and the Swiss Federal Institute of Technology (ETH), Zurich, before returning to the DKFZ in 2019 to establish her own group.
She’s now aiming lutetium-177 at triple-negative breast cancer. Its aggressive cancer cells lack receptors for estrogen, progesterone, and HER2, offering conventional radiopharmaceuticals nothing to latch on to.
Instead, her team is targeting a more obscure receptor found on these cells, called KISS1R. In collaboration with Bayer, the researchers developed a peptide called KiSS-34 that binds strongly to the receptor and helps deliver gallium-68 for imaging studies or lutetium-177 as a potential therapy.
Benešová-Schäfer is also working with α-emitting radionuclides such as actinium-225. The α particles carry much more energy than lutetium-177’s β particles, which means they can inflict greater damage on cancer cells. Another advantage of actinium-225 is that it decays into daughter isotopes that also emit α particles, delivering multiple punches to the cells. But these daughters can escape from the targeting molecule and stray into healthy tissue, potentially causing side effects.
To better understand those off-target effects, Benešová-Schäfer’s team developed a purification column that supplies francium-221, the first of actinium-225’s progeny. This has enabled mouse studies to track where francium and another daughter, bismuth-213, end up in the body.
The commercial success of Pluvicto and another lutetium-based drug called Lutathera has drawn billions of dollars into radiopharmaceutical research. Benešová-Schäfer says that the boom has created an urgent need for skilled radiochemists. So, in addition to creating cancer-killing drugs, she’s nurturing scientists with the know-how to harness radioactivity for good. “One of the most important parts of my work is to bring another generation of students toward our field,” she says.
