cancer genomics


How Personalized is Personalized Medicine? Krister Wennerberg on FIMM’s Individualized Systems Medicine

Most of the time, when we talk about personalized medicine, it’s not that personalized. What we’re really talking about is population-based medicine. However, there is a growing number of clinical/research groups around the world, including the folks at the Finnish Institute for Molecular Medicine (FIMM) who are combining an older method of functional profiling with new molecular profiling to come up with what the Fins call 'Individualized Systems Medicine.'

Krister Wennerberg joins us today from FIMM where he is the leader of the Cancer Chemical Systems Biology Group. He says that traditionally in our industry there has been two factions: one that has been focused on molecular profiling— which, he says, is leading today—and another group which is focused on functionalized testing, or seeing how the individual cancer cells respond to drugs through ex-vivo screening. This second approach has been around for some time but hasn’t been that successful. These two factions have been somewhat opposing each other.

“I don’t think that’s the way to think about it,” says Krister. "We really need to merge these together, and that’s how we’re really going to make advances. We need to start with the functional responses, and then try to lead back to what are the molecular drivers of this response."

Part of the special approach at FIMM is to use a new, more precise method of liquid handling for their screening which gives them greater quality control and the ability to make the most of each sample.

Digital PCR Opens Up New Liquid Biopsy Opportunity in Melanoma Treatment: David Polsky, NYU

The history of science is also a history of toolmaking. And nowhere is this more true than in modern biology. New instruments in the lab allow biologists additional modes of discovery, new levels of quantification, and the opportunity to pursue new and old questions with more data.

David Polsky is a dermatologist and researcher at NYU’s Langone Medical Center. Last week he received a grant from the NCI for readying a new liquid biopsy test that tracks the progression of melanoma for the clinic. Until now, there has been no blood based marker that was able to track melanoma as there is with other cancers such as prostate cancer and the PSA (prostate specific antigen) score. This new test, which could be a major breakthrough for the treatment of melanoma, targets seven mutations which occur in 70% of melanoma patients. These mutations are found in cell free, circulating tumor DNA.

In today’s interview, David points out that the test is possible only with the advent of digital PCR and its ability to measure DNA more with absolute quantification and sensitivity. We knew these mutations before, but just couldn't measure them.

“Droplet digital PCR has been a major breakthrough in our ability to detect rare events and also to quantitate them with accuracy and precision. Those two features are absolutely critical,” says David.

David and his group have been collaborating on the test with Bio-Rad, who makes the ddPCR instruments and designed these tests, and with Molecular MD. Clinical trials with Bristol-Meyers Squibb are expected. Now, with the preliminary science published, the NCI grant will go towards developing analytical and clinical validation so that the test might be commercially available for patients soon.

August 2016 with Nathan and Laura

It’s the end of summer and end of another month. Joining us to discuss the genomics headlines of August are Laura Hercher and Nathan Pearson.

A recent study demonstrating that breast cancer patients with low genomic risk may not need chemotherapy is just what precision medicine is all about, isn’t it? Theral and Laura think the study is a big deal. Nathan’s not so sure.

Nathan is convinced though that Eurocentric studies have implicit racism. Laura agrees, saying the lack of racial diversity in biological databases is a major weakness that we must face head on.

Also, the FDA issued a report supporting Oxitec’s GM mosquitos for use in Florida. Laura is on board with the science but warns about smugness on the part of the scientific community. And George Church’s lab released a reengineered e. coli. Nathan imagines a new genomic language of 2 letter codons.

A Precision Medicine Platform Comes of Age: Jonathan Hirsch, Syapse

Today’s show with Jonathan Hirsch, the President and co-founder of Syapse begins a couple years ago. We first featured him on the program in January of 2014 with the headline, Is this the Omics-to-Clinic Site We’ve All Been Waiting For?

It turns out, in many respects it is. Syapse has had some big wins with some of the more progressive healthcare companies in the U.S., including Intermountain and Stanford. This year Syapse announced the creation of the Oncology Precision Network for data sharing in cancer care among several major institutions. The company even got a shout out from Vice President Biden in one of the recent White House confabs.

Over the years we’ve featured various bioinformatics and clinical informatics companies who had the aim of bringing omics data to the clinic. Syapse is emerging as a leader in that field demonstrating strong traction, particularly in cancer care. Today Jonathan explains the company’s Precision Medicine Platform, on top of which sits their oncology application.  He gives an example of just how this platform is changing cancer care at Intermountain in St. George, Utah, a small town with some big expertise.

And has the Veep’s Cancer Moonshot been changing things up?

“Everyone focuses on the money, but it’s not about the money,” Jonathan says. "It’s about how you use the power of the presidency to knock heads together and bring people together in collaborative relationships that they might otherwise not have entered. We’ve seen a measurable change in attitudes around clinical data sharing from this initiative."

Know Then Thyself: Kari Stefansson, deCODE genetics

Kari Stefansson is a name well known in the field of human genetics. His founding of deCODE genetics in his native Iceland in 1996 took our field into a new frontier with the unique opportunity to work with not only a homogenous population but also to integrate with a large centralized healthcare database. It also surfaced a huge ethical debate about genomic privacy.

We’re very happy to welcome Kari to the program for the first time to talk about his vision for deCODE now that the company has been bought by Amgen. The company has continued to publish papers revealing major findings of rare variants associated with common diseases. Just last month Kari and deCODE published a paper in the NEJM with the discovery of a gene called ASGR1. The gene lowers the risk of heart disease by a substantial 34%.

Kari is passionate about discovery for the sake of discovery.

“All life on earth is rooted in information that lies in the simple code of As and Gs and Cs and Ts of DNA,” he reminds us. “Some of our discoveries are knowledge for the sake of knowledge. It is man studying man.”

But he also points out that as soon as they made the discovery of the ASGR1 heart-protective gene, researchers at Amgen went to work immediately on a drug discovery program. And, he says, he knows that many other pharma companies have already begun similar programs.

deCODE is perhaps best known though for their project to create a genomic database unlike any in the world. And for the ethical issues this has brought up. Last year deCODE announced that they had sequenced enough individuals to impute the genomes for the entire population of Iceland. This could lead to a new kind of preventative healthcare system that would be a model for other countries everywhere. It’s also left Kari and his colleagues scratching their heads over whether, for example, they have a social obligation to find out who in Iceland carries the dangerous BRCA mutations.

He shares some dramatic statistics that reveal their dilemma:

"Women who carry this mutation have 86% probability of developing a lethal cancer. They have 72% probability of developing breast cancer. They have a life expectancy that is twelve years shorter than non-carriers. They are three times more likely to die before the age of 70 than the non-carriers. And most of this risk could be mitigated by preventative surgery, for example.”

The interview goes well over our typical target of 20 minutes. But Kari is a deliberate thinker and an eloquent speaker. Enjoy.

Bringing Home Some Diagnostics Gold: Brad Gray, NanoString Show How It’s Done

You hear it everywhere. And it’s getting old. That "diagnostics is a tough slog.” That it’s the “redheaded stepchild of healthcare.”

And today’s guest doesn’t disappoint, repeating both these phrases. But Brad Gray and NanoString can claim some big “slogging" success. They’re coming out on top in diagnostics through some clever business strategy built on a solid platform. Made CEO at just 33 years of age, Brad has taken NanoString public and overseen a successful expansion from the research to the clinical market.

In his interview, you’ll hear Brad lay out the three pronged approach at NanoString. Starting as a spinout from Lee Hood’s Institute for Systems Biology, the company began in the life science tools space with their nCounter platform. The machine proved a favorite for cancer researchers because of its ability to look at single molecules of nucleic acid. When the company pole-vaulted into the clinical space, rather than set up their own lab and do the testing themselves--such as diagnostics pioneers, Myriad Genetics and Genomic Health--NanoString opted for a decentralized model. They did just the kind of thing that makes the FDA happy. They created a “push button simple” platform with kits so that clinical labs could do the testing themselves in a highly reproducible fashion.

But that’s not all. Under Brad’s leadership, the company has made several major companion diagnostics deals with big pharma. An agreement with Merck announced earlier this year delivered NanoString an upfront payment of $12 million. That’s a nice boost for a diagnostics company slogging away at reimbursement.

“The Merck deal is especially exciting because it’s the first major molecular diagnostics partnership in the field of immuno-oncology,” says Brad. "And the scale of it makes it the largest companion diagnostics deal ever announced, in economic terms.”

And what of the reimbursement slog for theirs flagship Prosigna breast cancer assay? NanoString can now boast Medicare coverage in all 50 states.

That’s about as good as it gets in our industry.

When Do We Move to Population Based Cancer Screening for Those with High Genetic Risk? Josh Schiffman, U of U

Last year when we were promised a soon-to-be-on-the-market, pan cancer, genetic based screening test, many of us were taken aback at the hubris. Not only does the science have a ways to go, there are deep ethical conflicts to work through. However, cancer screening based on a patient’s genetics is already being done in certain niche areas.

Josh Schiffman is a cancer researcher at the Huntsman Cancer Institute in Utah. He’s also a pediatric oncologist serving as the Medical Director of the Institute’s High Risk Pediatric Cancer Clinic. At the clinic, Josh and his colleagues put out a study where they demonstrated that early cancer surveillance in patients who have a rare disease called Li-Fraumeni Syndrome can dramatically increase overall survival.

Why Li-Fraumeni Syndrome? It turns out that patients from families with Li-Fraumeni Syndrome have only one working copy of the P53 gene, a well known protective mutation for cancer. Because of this genetic predisposition to cancer, these patients were screened early with whole body MRIs and other blood tests. For the study, patients whose tumors were found due to the early cancer screening were compared to those patients whose cancer was diagnosed because they presented with symptoms. The overall survival rate for those screened early was 100 percent compared to just 20 percent in the later group.

Should Josh’s work with this sub-population translate out to doing cancer screening for all based on known high risk cancer mutations? Josh says let’s do the study. As for the ethical concerns, he feels the landscape of cancer genetics has shifted.

“Many years ago we didn’t offer P53 screening to children, because there was nothing you could do about it,” he says in today’s interview. "But now that we’ve come a far way and technology has improved, if there is something we can do about it, then it makes more sense to do the test. So we believe very strongly that all children at increased risk [for cancer] should be tested."

The Solid Future of Liquid Biopsies with Michael Nall, Biocept

There’s been lots in the news this past year about liquid biopsies—those non-invasive tests which locate biomarkers in a vial of blood. Much of that press (perhaps too much) has been about using these blood tests for cancer screening: predictive tests that could be available to consumers some time in the future.

But according to today’s guest, the real news about liquid biopsies is that they are in use now. Michael Nall is the CEO of Biocept, a company based in San Diego which has gone about as far as any organization in commercializing these non-invasive tests. They offer tests for many kinds of cancer, including breast, colon, prostate, and lung.

“The area we’re focused on really hasn’t gotten as much attention [as the cancer screening tests]. And yet it’s the nearest term and the biggest unmet medical need today: how do you help patients who have been diagnosed with cancer and who are progressing?” says Michael in today’s interview.

Biocept stands out in the space for not only their comprehensive line of testing, but for their demonstration of just how to commercialize these tests. The company has thirteen salespeople around the country who call directly on clinics. They are focused on two niches: cases where the cancer has metastasized in the bones or the brain and cases where not enough or no solid biopsy can be obtained.

Most importantly, Biocept has succeeded in getting paid for their tests using the same existing CPT codes that are used for the solid tumor tests.

Will we soon see a time when the liquid biopsy is the preferred test? How is Biocept preparing for impending FDA regulation? Hear this early success story for a pioneer in a rapidly growing field.

Digital Pathology at Scale: Epic Sciences Takes CTC Technology to the Next Level

It’s the beginning of the age of liquid biopsies, when less invasive, regular blood draws will provide more information than the occasional solid tissue biopsy. Companies that offer tests based on circulating tumor cells or cell free DNA in the blood are popping up like genome interpretation companies were a few years ago. As our understanding of biology at the molecular level advances--particularly in the field of cancer research--the more this practical and focused approach for teasing out the information in the cell, in the body gains steady adoption.

The success of prenatal diagnostics with a small amount of blood from the mother has shown us—and investors—that there’s there’s a wealth of information and money to be made from blood samples. And the promise of a non-invasive procedure to provide more important data than traditional biopsies can seems too good to be true.

Yet, we’re still in the early days. Few liquid biopsy tests have been commercialized. Today’s guest, Murali Prahalad, is the CEO of Epic Sciences. They are touting a new platform for analyzing circulating tumor cells, or CTCs. This has been a tricky space for companies (remember On-Q-ity?), so the big question for Murali is what makes Epic better?

Murals says that previous CTC technologies made some "grounding assumptions," such as that the cells had to have surface proteins used to isolate them, or that they had to be larger in size than the surrounding white blood cells.

“What we’ve said is let’s admit we don’t know what we don’t know. So let’s shotgun this. Let’s look at all the nucleated cells and get them on a proprietary glass slide and then use a mixture of staining, imaging, and computation techniques to really figure out what’s cancer from normal. So we’re not making any grounding assumptions here. And what it’s done is reveal a far greater range of these species in the blood than we ever thought possible. . . . We let the biology reveal what we should be worrying about.”

That all sounds fair and good. Now how will Epic take their latest studies and commercialize them into clinical assays that doctors can use?

For inspiration, Murali draws on the history of HIV drug development. It is now customary for AIDS patients to keep regular counts on their viral load as they manage their illness with one pill a day. This type of regular screening using just blood samples could become the norm in cancer as well. Quoting Mark Twain, Murali says, “history may not repeat itself, but it does rhyme."

January 2016: Landergate, Grail, and Cancer Moonshot

“It being the month of Hypeuary, go hither through break in yonder wall called LanderGate, and thou wilt be on route to reach the Grail. Drink from this to find your Cure, and Death shall haunt you even more.” -Pithy Monton

Today we do something a little different. We’re joined by two commentators to look back over the past month’s headlines. Laura Hercher is a genetic counselor on the faculty at Sarah Lawrence College. She’s also a regular contributor to the DNAExchange blog. Nathan Pearson is the Senior Director of Scientific Engagement and Public Outreach at the New York Genome Center.



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