This is the first in a series of articles featuring biopharma experts from Stanford University. The articles are sponsored by Stanford, and independently reported by BioPharma Dive staff.
In 2001, the FDA approved Novartis' Gleevec (imatinib) for the treatment of chronic myelogenous leukemia (CML), a rare white blood cell cancer. It was a watershed moment—in the years since, physicians and scientists have come to hail Gleevec as a "miracle drug" and "silver bullet" that revolutionized the treatment of a blood cancer that comprises about 14% of all leukemias in the West.
But beyond its immediate benefit for CML patients, who enjoy a stunning 89% complete hematalogic response rate to the treatment even five years out, Gleevec was revolutionary for another reason: its very action mechanism, which inhibits a tumor-inducing kinase that is only present in CML patients' cancerous cells. Since that genetic abnormality occurs only in the cancer cells, Gleevec is able to target them without killing off healthy blood cells and causing the types of agonizing side effects associated with more heavy-handed and toxic treatments like chemotherapy.
"This drug really extends life for people who were facing almost certain death," said Stanford University's Dr. Michael Snyder in an interview with BioPharma Dive. "That's the poster child for personalized medicine."
Snyder would know a thing or two about that—he's chair of the genetics department at Stanford and director of the university's Center for Genomics and Personalized Medicine. And he and Dr. Barry Starr, another Stanford geneticist who heads the university's Stanford at The Tech scientific outreach program, say the best is yet to come in the personalized medicine and genomics revolution.
The cutting edge of genomics
Stanford has been at the forefront of the genetics, genome sequencing, and personalized medicine movement for years. "[W]e've invented a lot of genomics technology for capturing peoples' genome," said Snyder. "We also do quite a bit of cancer genome sequencing and also sequencing on a lot of undiagnosed diseases."
Stanford's been so successful on the research side of the equation that it's even launched a professional online Genetics and Genomics Certificate program for the non-scientist, non-grad student crowd, including sales reps, venture capitalists, R&D teams, doctors, and a variety of other stakeholders in the medical and life sciences sectors. Applicants simply need five years' work experience, a bachelor's degree, and a high school-level knowledge of biology and chemistry in order to enroll in the six-course program and learn about "big picture" issues in genetics, genomics, and personalized medicine.
A new standard of care in cancer
Starr offers a bold take on the not-so-distant future of U.S. healthcare: "Certainly, within a decade, I think everyone will have their complete DNA sequenced."
This is particularly significant for cancer patients, who have even more to gain from sequencing their genomes as scientists' understanding of cancer's mechanisms continue to evolve.
"In the last several years, as we've started to sequence cancer genomes, it's become this whole new field," Snyder explained. "It used to be classifying cancer based on tissue of origin, like ovarian or breast cancer or colon cancer. But it's becoming increasingly clear that cancer is better classified by the genetic mutations that arise."
That means that cancer has come to be seen, in essence, as a genetic disease that also requires gene-based treatment options. "There's thought to be somewhere on the order of 10 or 20 mutations that will cause cells to grow uncontrollably—so 10 to 20 mutations per cancer," said Snyder. "So what people discovered by sequencing the genome of cancer DNA is that the genes that are altered vary from patient to patient, and it's very difficult to predict who will be changed for what. It's really only discovered when you sequence the DNA."
"It's going to become standard of care. When you get cancer, you'll get your genome sequenced."
Better, and better-targeted, drugs
The genetic revolution is promising not only for its capacity to inspire new drug pipelines and treatment options, but also for its potential to shed light on how these treatments can be better-targeted.
Snyder points to a relatively recent example involving non-small cell lung carcinoma (NSCLC) and colon cancer. Scientists used to think that a mutation in the EGF (or HER1) receptor, a growth control gene, was characteristic of NSCLC. "But it turns out, if you sequence a colon cancer, as we did recently for a metastatic colon case, that person was also amplified in the [EGF gene]," said Snyder.
"And it's pretty clear, then, that that person should be put on a drug that targets that particular genetic change, rather than some other traditional colon drug that people would use."
A more targeted approach means medications with less side effects and more substantial therapeutic benefit—such as Amgen's Vectibix (panitumumab), a monoclonal antibody which specifically targets EGF in colorectal cancer patients. And it's an approach that's here to stay.
"Treatments are being prescribed in a much more specific, and much more targeted therapeutic sense for the individual," said Snyder. "And that's why it's called personalized medicine."
Heading toward a "Gattaca" future?
One of the major reasons that cancer is an ideal target for personalized genomic therapy is its distinctly genetic nature. Genes such as the HER1 gene, or the BRCA genes that foretell breast and ovarian cancers, may be easily identified via diagnostics and eventually treated.
But what about tackling other diseases like diabetes and heart disease—or, given Starr's prediction of a future where everyone has their genome sequenced, predicting more fundamental characteristics like IQ based on genetics alone?
"I think certainly we'll all know who our real dads are, because that's an unintended consequence of these genetic tests," said Starr. "But in terms of medicine... we will certainly know all of the simpler genetic diseases that we carry, such as cystic fibrosis, BRCA1, sickle cell anemia—those common single gene disorders [within the next few years]."
And more long-term?
"Within 10 years, we might be able to get into the more complex diseases—maybe, maybe not, in terms of heart disease, diabetes, perhaps Alzheimer's—to try and figure out our risk factors and what we can do specifically to decrease our risk," he said.
But Starr says no one should expect a world like that of Andrew Niccol's 1997 sci-fi movie "Gattaca," wherein a person's lifespan, intellect, and propensity for mental illness can all be predicted via a simple genetic test at birth.
"I actually don't think we'll ever understand it well enough to get there," Starr says, laughing. "The genome is just hideously complex, and... it's surprising how personalized everyone's genome is. You may get diabetes for a different set of genetic markers that run in your family compared to someone else."
At the end of the day, even a sample the size of the entire human population isn't enough to work out certain genetic algorithms. "In a Gattaca world you could probably figure out how intelligent you're supposed to be—that's hundreds or thousands of genes with, you know, tens or hundreds of variants. And if you do the math, then seven billion people isn't really enough to figure it out, something of that complexity," explains Starr.
It appears that mankind will have to settle for a future in which some of the deadliest diseases on the planet are treated with personally tailored scalpels—rather than the medical equivalent of a buzzsaw.