Technology Powers Bioscience in Fight Against Cancer
How one man is staying ahead of his cancer by finding the genetic factors that fuel it.
The thought of leaving behind his wife and seven-year-old daughter is driving Bryce Olson to the edge of life sciences, where computational analysis of human DNA is pushing bioscience and healthcare into a new era of precision medicine.
“When my doctor told me I had prostate cancer, those two words turned my world upside down,” said Olson.
In spring 2014, at age 45, Olson was diagnosed with stage 4 metastatic prostate cancer, which has a five-year survival rate of just 28 percent.
Olson is one of 2.8 million Americans now living with the disease. The average age for being diagnosed with prostate cancer is 66, according to Cancer.org.
“The stats for people like me are gloomy, but I’m set on staying ahead of it by finding the right treatments that will slow down or even stop my cancer,” said Olson.
He has been through prescribed surgery, hormone therapy and chemotherapy treatments, all of which temporarily wrestled his cancer into submission.
It’s a matter of time before his tumors begin to grow again, so he’s leaving no stone unturned in his fight to stay alive. It’s a fight he believes will benefit others living with cancer now and in the future, especially if they better understand the new world of personalized, molecular treatment.
Olson is a global marketing director at Intel, a place that’s seen its share of brave people fight against diseases. Former CEO and Chairman Andy Grove was diagnosed with prostate cancer in 1995 and the following year wrote a Forbes’ cover story “Fighting Prostate Cancer,” which outlined his analytical approach to finding the right, state-of-the-art treatment.
Eric Dishman, an Intel Fellow and general manager of Intel’s Health and Life Sciences, was diagnosed with two rare kidney diseases at age 19. After trying a variety of treatments, he underwent a successful kidney transplant in late 2012.
A long-time surfer, Olson sees himself dropping into a giant peak-shaped wave, where the forces of technology and bioscience are coming together to help improve early detection and attack advanced cancer.
In his fight against cancer, the Oregon resident decided to have his tumor DNA analyzed to gain better understanding of his cancer at a molecular level. By uncovering the cause of his aggressive form of cancer, he hopes to find clues that will lead to the right treatment.
“Genomic sequencing will help guide my future treatments,” Olson told iQ. “Unfortunately most people with cancer have no idea what specific genetic mutations are actually fueling their unique cancer growth, and not knowing that is dangerous.”
He had his tumor analyzed at the nearby Knight Cancer Institute at Oregon Health & Science University (OHSU), which helped pioneer personalized medicine and is an international leader in research and cancer treatment. OHSU is working with Intel to use high-performance computing and cloud technology to speed up and lower the cost of analyzing DNA, so that precision care becomes the standard for treating diseases.
DNA, or deoxyribonucleic acid, is the chemical that carries instructions to cells in the body. Chromosomes from each parent combine to create a person’s genome, which consists of six billion individual DNA letters.
When chemicals that carry instructions deviate from the norm, cells can grow out of control and mutate. Mutations can be inherited or triggered by environmental factors or lifestyle choices. Typically it requires several different mutations to result in cancer.
Genome sequencing is the process to figure out the order of those individual letters that make up a person’s DNA.
While gene sequencing at birth or an early age could help people understand their own health risks and potential health risks of family members, until now the process has been used primarily for people diagnosed with terminal diseases.
Sequencing presents huge promise, but it has yet to spark a widespread revolution in healthcare outside of leading cancer institutions, according to Christopher Corless, M.D., Ph.D., director and chief medical officer of the Knight Diagnostics Laboratories, which are part of the OHSU, Knight Cancer Institute.
“There is a fundamental shift underway, but it’s incomplete,” Corless said. “Only some people understand genes and the implications of mutations. Democratizing this is a ways down the road.”
At academic centers sequencing is becoming more routine, but not yet at smaller clinics and hospitals, he said. The challenges include costs, insurance reimbursements and the proper medications for targeting those mutations.
This is where Olson finds himself, between a hospital treating him using traditional means and a research facility that is helping him uncover more precisely what’s driving his tumor’s growth, and to work this into clinical decision making.
Even if sequencing helps analysts find the problems, there may not be an FDA-approved medication that meets Olson’s specific needs. But sequencing may help doctors find a new clinical trial in which Olson could be offered an experimental drug that could be the best treatment option for his specific disease.
While this may seem an uphill battle, it’s not insurmountable, according to Dr. Brian Druker, M.D., director, OHSU Knight Cancer Institute.
“When we understand what is broken, we can fix it,” Druker said.
Druker’s research nearly 20 years ago led to the development of Gleevec, the first molecular targeted drug able to kill cancer cells while leaving healthy tissue unharmed. It was first used to fight chronic myeloid leukemia, but has since been determined effective in treating about 10 types of cancer.
Controversial at the time, Druker’s specific targeting of a cell’s mutation is leading to molecular treatments that, for many, are less toxic than carpet-bombing therapies like chemotherapy.
Druker said we can defeat cancer. It requires knowledge, and computer technology is accelerating that collective understanding.
“The first human genome was sequenced in 2001,” said Druker. “It took about 10 years and cost $100 million. Today, a person can have their DNA sequenced in about four weeks for about $1,000. We have a remarkable ability to generate data and it keeps improving.”
Each time someone gets their full genome sequenced, it generates information for 30,000 genes, which means terabytes of computer data. Analyzing that data into meaningful, actionable results is expensive and time consuming.
The notion that everyone is unique could lead to a future of infinite complexity, creating a Sisyphean task for medical scientists and doctors who need to make sense of all of this data. However, Druker believes that as more genomes are sequenced, patterns will emerge.
“Computation will make it clear,” said Druker. “It will help us more rapidly identify which drugs will help. It will take days to weeks instead of years.”
And if no drug exists and there’s a significant need for it, pharmaceutical companies can start working on those right away.
In Olson’s case, searching for precision treatments that go after his specific mutations is where he’s focused now.
“Things are more clear and at the same time more scary now,” said Olson.
“Most prostate cancers feed off of testosterone. They are stymied by therapies that either reduce the level of testosterone in a guy’s body or prevent the cancer’s cell’s receptors from binding to testosterone,” he said.
Sooner or later his prostate cancer will learn how to survive and grow even in low- to non-existent circulating testosterone levels. It feels like he is in no-man’s land because there are very limited FDA-approved treatments for fighting prostate cancer that resists hormonal treatments.
“Genomic sequencing opened my eyes to something called the PI3K signaling pathway that actually drives resistance to hormone therapy and stimulates tumor growth. It’s scary knowing that my tumor appears to be using that actual pathway to grow.”
To Olson, this discovery means that he needs to avoid spending time and insurance money on population-based treatments, which don’t impact his specific needs. Instead, he and his doctors will spend more time getting him on clinical trials for experimental treatments that could attack his cancer more precisely.
Nearly 12 people die from cancer every minute, leading to more than 1,700 deaths each day, according to World Cancer Death Clock. Cancer accounts for one in seven deaths worldwide. In the United States, Cancer is the second-most common cause of death, exceeded only by heart disease, and accounts for nearly one in every four deaths.
According to Corless, today’s gene sequencing focuses on panels of genes that are known to play a role in cancer. This type of sequencing zeroes in on the most important information needed urgently.
“In our first foray into using modern sequencing, we’d look at 23 to 76 genes, depending on the cancer,” said Corless.
He said that this kind of targeted sequencing has generated a lot of data and has helped many patients. It can find mutations that are interesting and important in 50 to 60 percent of patients.
“Today, targeted sequencing has a potential impact on patient care in about 20 percent of cases. We think that number will go up when we go to exome sequencing.”
He and his team at OHSU are now shifting from focused panels to broad-based, ‘whole exome’ sequencing that looks at all the protein-coding regions of the genome (about 1.6 percent of the total DNA).
“We are scaling up from an average of 50 genes for one patient to an average of 20,000 genes,” said Dr. Corless. “It’s a massive step forward.”
Gene sequencing is accelerating the availability of new treatments beyond chemo, he said.
“There are 500 different compounds in clinical development. Some are being developed in conjunction with universities, others in conjunction with pharmaceutical companies.”
Using genomic sequencing in the treatment of cancer has profound implications for the future of cancer patients everywhere. Instead of throwing darts at a blank wall, as Olson puts it, doctors and patients will be able to learn what drugs successfully treat what mutations.
OHSU’s work with Intel to build a huge database or so-called “cancer cloud” could allow researchers in Oregon to privately share critical information with doctors across the nation and around the world.
“This will one day become a reality for all patients, where targeted therapies can attack the genetic abnormalities that are driving a person’s cancer and stop the tumor in its tracks,” said Olson.
For now, Olson is navigating new ground that he believes could lead to identifying new drugs or help doctors find the right combination of drugs to halt his cancer.
“I’m going to fight this thing as long as I can,” said Olson.
“If it does take me down, I’d like to think that my efforts are accelerating personalized cancer care opportunities for others. This experience is showing me and my family how critical new technology and gene analysis are to our lives.”