Precision Medicine: Little Benefit So Far, But Lots of Hope

There was one boy, eight years old, who Olena Morozova thinks about still.

He was being treated for sarcoma, a rare cancer found in bones or connective tissue. A genetic mutation was found that might partly explain his illness, but there was no therapy to fix it.

“So the patient was back to square one. Even though he was in the trial, there was nothing that the trial could do," says Morozova, the principal researcher in the California Kids Cancer Comparison. The project attempts to find treatment for children who haven't responded to standard therapy, by analyzing the genetics of their tumors.

Morozova's team had developed a tumor map, a graphical representation of how different or similar individual tumors are at a molecular level. Curiously, the boy’s tumor was genetically similar to another type of cancer called neuroblastoma, which is treated with a particular therapy considered to be ill-suited for sarcoma.

Out of options, the doctors gave it a try.

"The patient had a partial response," says Morozova, "It wasn't a complete remission, but just the idea that somebody could benefit from this analysis and we could learn something new was very exciting for us as a bioinformatics institution."

More analysis, another drug, sending the tumor into remission for several months. That gave the boy back something resembling a normal childhood. He ran, he played. His appetite returned.

But the tumor proved resilient.

In January, the boy died.

Amidst the tragedy, Morozova and her researchers found something  to be hopeful about: His temporary recovery showed them their project possessed greater potential to help patients currently fighting disease.

It "started us on this vision," she says. "In the beginning we started out as just a research project. We didn't think that this would be immediately of clinical benefit to patients."

Now, the California Kids Cancer Comparison gets involved on an individual level, participating in the tumor board at Stanford Hospital, sharing their results with panels of experts from different medical specialties who decide, together, on treatments for patients.

Results Not There Yet

Still, the death of group's child patient points to an unhappy reality: What we call "precision medicine" -- tailoring treatments according to the genetics, environment and lifestyle of individual patients --still  isn’t precise enough. And our growing knowledge of the genetics of cancer has yet to save many lives.

The concept of precision medicine grows out of a longstanding frustration in tackling disease: Some patients just do not respond to a treatment that normally works. Not only does this failure necessitate a different remedy, it also puts someone who is ill through a costly and often painful process for no benefit.

Being able to choose the right treatment from the start would be an enormous advance. The government is on board. The 2016 federal budget includes $215 million for the Precision Medicine Initiative. A major part of the project is the creation of a "national research cohort," a group of volunteers willing to share their genomes and daily living habits with researchers from the National Institutes of Health as part of a 10-year study.

In the nation’s most populous state, Gov. Jerry Brown has supported the launch of the California Initiative to Advance Precision Medicine. But so far, public and private funders have dedicated just $3 million to the project. Still, the researchers at the California Kids Cancer Comparison, a pilot project of CIAPM, aren’t complaining.

"Pediatric cancer research is very poorly funded," says Isabel Bjork, director of the Cancer Comparison. "It's a demonstration project -- that was important for us, because we had some theories that we had seen work a few times, but we need bigger comparisons to really test them."

Many hospitals are conducting their own precision medicine trials, sequencing genetic information from their patients and their patients’ tumors in the hopes of finding an "actionable mutation" that might respond to a treatment.

The results to date have been underwhelming. "In the majority of the clinical trials, the benefit has been very small, measured as two months of longer survival," Antonio Fojo, an oncologist at Columbia University reported at the American Association for Clinical Chemistry in July.

'Let's Change This'

When President Obama said in his 2015 State of the Union Address that the national initiative would "bring us closer to curing diseases like cancer and diabetes," some experts were skeptical. The interplay of genetics and daily life habits are too complicated to figure out, they argued.

But for those who work with pediatric cancer patients, any medical advance, even the most incremental, is cause for hope.

Mariela Medina works at Jacob's Heart, an organization in Watsonville, California that helps kids with cancer, and their families, cope with the disease. Many of the children cared for by the organization are also part of the California Kids Cancer Comparison.

Medina specializes in working with teens, and she knows first-hand what they're going through. More than a decade ago, just before she turned 14, she was diagnosed with Hodgkin Lymphoma,‎ stage IV. She's been cancer-free for 10 years now, but not before a trio of relapses.

Her memory of her cancer years is foggy, something she attributes to chemotherapy, but from what she recalls, the treatment was rough, with bad nausea. "I couldn't keep anything down, I was on so many medicines," she says.

Lori Butterworth, founder and director of Jacob's Heart, says her hope is that researchers like Olena Morozova will put her out of business.

"I think of all the names and all the faces of kids who have died," she says, "and I think, 'There's been too many of them. Let's change this.' "