Few words chill the soul like “cancer,” a single-word diagnosis that heralds a battle of life and death. But beneath the pain and tumors and fear may be a single switch, a gene that turned the wrong way and activated a process it wasn’t supposed to.
Identifying that switch for each patient can change the way we think about, and treat, cancer, and the Providence St. Mary Regional Cancer Center is working toward that future.
Providence Health and Services — including Providence St. Mary — has joined a partnership with NantHealth and the Chan Soon-Shiong Institute of Molecular Medicine to develop a network of genomic analysis — studying both DNA and RNA inside a person’s genetic code — and proteomics — studying proteins produced by genes. Providence is moving these techniques from research facilities into clinical treatment, using the tools to study a patient’s specific cancer and provide tailored treatment options.
Dr. James Cunningham, medical director of Providence St. Mary Regional Cancer Center, said doctors generally rely on the location of the tumor — lung cancer vs. throat cancer, for example — and how the cancer looks under the microscope to recommend treatment. But now, through whole-genome testing, doctors can add a molecular dimension to understanding a patient’s specific cancer.
“When we look at cancers and classify them based on how they look under the microscope, we get a certain hierarchy of treatments. Genomic testing tells us the commonalities they have in the genes that might not be apparent from the (physical) testing,” he says.
For example, a stomach cancer might have more in common with a skin cancer at the genetic level. Instead of treating that cancer like a typical stomach cancer, doctors can prescribe a medication they might have overlooked because of the location of the cancer. This means a cancer that might have been treated through chemotherapy could instead be treated with a less invasive, more targeted medication.
In addition to providing treatment options for the specific patient, the sequencing will help boost existing data on cancer mutations. Researchers have been compiling “atlases” of recorded genomes, activating genes and cancer implications, but the ability to use that information in a clinical situation is new. Under the Providence program, doctors could see how a medication affected a patient with a similar cancer, and use that information in their treatment of another patient.
The procedure has widespread implications for science, but Cunningham says most patients take a more pragmatic approach, asking about effectiveness, side effects and cost. Mapping a genome currently costs about $1,000, but Cunningham expects the procedure to become less expensive as technology improves. He pointed to an example of how technology is the driving force behind bringing this process from the research lab into the cancer center.
“When sequencing was first done, laboratories might dedicate a year to sequence a single genome. Now we do it all in an afternoon,” Cunningham said. “That’s amazing.”
To complete the whole-genome testing, a sample of the patient’s cancerous material — either from a previous biopsy or a new procedure — is taken, sealed in a paraffin block and sent to the testing center. There, the genetic material is removed from the block, and the DNA is extracted and separated into a single strand. The strand is then chopped into fragments for sequencing, where a computer scans all the fragments, looking for and documenting mutations.
Cunningham compares the process to editing a book. If the patient’s whole genome is made up of all the words and sentences in a book, each fragment is comparable to a sentence, and each genetic mutation is similar to a misspelled word.
“Let’s say you took a sentence from a book and spelled out all the letters in all the words in that sentence, looking for any spelling errors. Then, imagine if that book had 30,000 sentences, and we’re looking for spelling errors in every one of them,” he said. “We’re looking for spelling errors that we have a treatment for.”
In the case of genes, those spelling errors act as molecular switches, activating in ways they should not, like a machine with its switches stuck in the “On” position or a computer program with an unresolved glitch. Identifying the switches is the first step, and can lead to a match with a targeted treatment. Cunningham says whole-genome sequencing works especially well for some cancers, such as lung cancer, where pharmaceuticals are available to combat the specific mutation.
Just identifying the switches, however, does not automatically guarantee the patient can avoid chemotherapy and traditional treatments.
Often, the mutations identified in the sequencing will not have a commercially available corresponding treatment. But, even in such cases, they might point to a pharmaceutical that, though not yet approved, shows promising results in clinical trials. A doctor cannot write a prescription for a drug in a clinical trial, but can present the patient with the option.
In its first three months of testing, St. Mary has pointed two patients to clinical trials based on their whole-genome sequencing. One patient chose not to participate in the trial at this time; another has opted to, and is a candidate. A third patient was prescribed a commercially available medication doctors would not have prescribed without the information provided by whole-genome sequencing.
In the early stages of its whole-genome sequencing program, the Cancer Center is focusing on patients with advanced cancer whose primary treatments have failed. Many of these patients are elderly and may have other health issues that make chemotherapy dangerous or impossible.
“These treatments are not yet ready to supplant chemotherapy,” Cunningham said, “but that day is coming.”
Cunningham says he looks forward to a time when he will be able to do whole-genome sequencing for every patient as soon as cancer is detected.
“Just think that we, a small community hospital, now have access to very state-of-the-art molecular testing that gives us profound information,” he says. “We’re very excited to be able to offer this.”