Discovering the gold standard of cancer drugs

Legendary figure skater Scott Hamilton has been diagnosed with cancer three times.

In 1997, Hamilton, who won gold at the 1984 Winter Olympics, was diagnosed with stage 3 testicular cancer, which had spread to his stomach.

When they told me, I was like, ‘I want it to be something else,’” Hamilton says. “But they said, ‘No, this is a good one to get, if you had to choose one,’ which is kind of crazy. But I’m grateful there was a proven treatment. I know many cancers don’t really have one.

That proven treatment was cisplatin. Created in 1844 by an Italian chemist, cisplatin’s use as a cancer treatment was discovered at Michigan State University in 1965.

The chemical compound—which prevents the DNA in cancer cells from replicating, confusing them and causing them to die—is used to treat many types of cancer, but is most widely prescribed for testicular, ovarian, bladder, lung and stomach cancers. With a cure rate north of 90 percent for testicular cancer, cisplatin has become the gold standard to which many new cancer medicines are compared.

This year marks the 40th anniversary of the anti-cancer drug’s approval by the Food and Drug Administration, an event significant to cancer patients and the medical community, but also to Michigan State University’s research legacy.

Celebrating an ‘aha moment’

Finding a cure for cancer is the holy grail of scientific research.

So when the late biophysicist Barnett Rosenberg emerged from his lab in the old biochemistry building at Michigan State in 1965 and proclaimed to a group of grad students, “I’ve just cured cancer!” it got their attention.

While not a cure, it was an “aha moment” that led to saving millions of lives.

After years of work and creative thinking, Rosenberg and his research partner, microbiologist Loretta Van Camp, had discovered something was causing cancer cells to elongate, but not divide—the first glimpses of cisplatin.

“They knew exactly what that meant,” says James Hoeschele, who later worked with the team on the discovery of carboplatin, an updated, less-toxic form of cisplatin. Rosenberg and Van Camp understood that this elongation interfered with DNA replication, killing the fastest-proliferating cells, which in theory are carcinogenic.

Yet, the process wasn’t smooth sailing from there.

When it came time for the independent replication of their results, the experiment failed. But Van Camp noticed the stock solutions used to host the bacteria were being bleached by the sunlight entering the windows of the new lab setting, thus causing the solution to become more concentrated. Something as simple as the existence of windows where none had been previously had changed the outcome of the experiment.

“It was a serendipitous moment,” Hoeschele says. “Loretta’s observation skills were exceptional.”

The scientists recreated the environment from their original lab and the experiment worked.

The team—which by then included graduate student Thomas Krigas, credited as the third co-inventor of cisplatin—spent the next five years injecting every possible variable that could affect bacterial growth into the experiment. They altered the physical conditions, including voltage, current and temperatures, as well as other variables to determine the causative agent before settling upon the precise compound.

The rest is cancer-fighting history. 

Fueling new research and discovery

The discovery, patenting and FDA approval of cisplatin—often called the “penicillin of cancer drugs”—was a 13-year process, an unusually brief period of time in the research world.

“These are home runs that happen very rarely,” says Richard Chylla, executive director of MSU Technologies, which facilitates the commercial development and public use of technologies and copyrightable materials developed by MSU faculty and staff.

“This is one of those handful of success stories where the impact of its discovery is far more important than the money the discovery made,” Chylla says. “Cisplatin has had a huge impact on society. It’s a cancer workhorse.”

Four decades later, cisplatin also is making new discoveries possible every day at MSU.

Royalties earned from sales of cisplatin and its derivative, carboplatin, fuel the work of and investments by the MSU Foundation—an independent, nonprofit corporation—through offices such as MSU Technologies. There, it supports investments in research and economic development initiatives through the commercialization of cutting-edge technologies invented by MSU faculty, staff and students.

“The fact that I work in an office that is the legacy of something like this is huge,” Chylla says. “The royalties allowed us to build capacity, fund research, do a lot of things, but when we look at the success of our office, we’re looking at what kind of impact we have. This discovery has literally saved millions of lives.”

Thriving after a cancer diagnosis

The discovery, patenting and FDA approval of cisplatin was a 13-year process, an unusually brief period of time in the research world.

 

“These are home runs that happen very rarely,” says Richard Chylla, executive director of MSU Technologies, which facilitates the commercial development and public use of technologies and copyrightable materials developed by MSU faculty and staff.

 

“This is one of those handful of success stories where the impact of its discovery is far more important than the money the discovery made,” Chylla says. “Cisplatin has had a huge impact on society. It’s a cancer workhorse.”

 

Four decades later, cisplatin also is making new discoveries possible every day at MSU.

 

Royalties earned from sales of cisplatin and its derivative, carboplatin, fuel the work of and investments by the MSU Foundation—an independent, nonprofit corporation—through offices such as MSU Technologies. There, it supports investments in research and economic development initiatives through the commercialization of cutting-edge technologies invented by MSU faculty, staff and students.

 

“The fact that I work in an office that is the legacy of something like this is huge,” Chylla says. “The royalties allowed us to build capacity, fund research, do a lot of things, but when we look at the success of our office, we’re looking at what kind of impact we have. This discovery has literally saved millions of lives.”