precision medicine


Single Cell Analysis Shows Important New Detail in Key Clinical Study of AML: Koichi Takahashi, MD Anderson

The history of biomedicine goes something like this:

  1. A new tool is invented. 2. New tool is used in research labs to generate new data and new hypotheses. There is new science. 3. New tool is used in clinical setting to confirm this new science with real patients. 4. Then new tool is adopted into clinical use.

All the buzz these days, single cell DNA analysis instruments have just made it into step three.

Today we talk with Koichi Takahashi, Assistant Professor in the Department of Leukemia at MD Anderson and author of the largest clinical study to date using single cell analysis in the study of AML.

For years physicians and researchers have been testing patients for well known cancer driver mutations such as KRAS and BRAF with next generation sequencing tools, or what are now being called “bulk sequencers.” Koichi points out today that new single cell analysis tools are allowing researchers to see the unique genomic environment that lead to the common driver mutations and may be responsible for why each patient responds differently to the same therapies. Knowing each patient's individual tumor genomic environment--and not just the final driver mutation such as KRAS-could lead to effective tailored treatment.

“The development of cancer cells is like Darwinian evolution. They are adapting to the selective pressure of the tissue ecosystem. And by looking at the single cell clonal architecture of the mutations, we can actually build a phylogeny tree of how a particular patient's leukemia developed—like even before they were diagnosed with leukemia. Over the years how this leukemia was created—this single cell DNA sequencing can inform us of this history.”

Is this new scientific understanding able to impact yet how Koichi is treating his patients? What is next for this technology and for the field of AML research and treatment?

Where I Agree and Disagree with Precision Medicine’s Chief Critic, Michael Joyner

Precision Medicine is more than a narrative, a story.  Hundreds of thousands of patients take drugs every day that are precision medicine drugs.  Thousands of women have been tested for BRCA genes and thousands of others diagnosed with lung cancer tested for EGFR mutations.  This has been more than a story for them.  It has saved their lives.  From rare disease diagnoses and therapies to the entire field of non-invasive prenatal testing, genomics has revolutionized medicine. 

Who Is Misleading Whom About Precision Medicine?

This month the New York Times put out an opinion article that was a reprint from Kaiser Health News written by Liz Szabo positing big doubts about the project of precision medicine. For the Times, it came with the title, “Are We Being Misled About Precision Medicine?” Unfortunately this piece does exactly what it warns against. It misleads.

Putting the headline in question form, rather than declaratory, reveals an insecure thesis. Why not just say it?

Should Biobanking Come Under CLIA? Shannon McCall, Duke

When former President Obama’s team released the paperwork for what’s become the All of Us Research Program, in the part about biobanking, the wording specified that the biobanks applying for the grants be “CLIA compliant.”

“They didn’t put quotes around it, but whenever I say it, I put quotes around it. “CLIA compliant”—it's not a thing,” says today’s guest Shannon McCall, one of our country’s leading experts in the field of biobanking and biospecimen science. Shannon leads the Precision Cancer Medicine Initiative with her team at the Biorepository and Precision Pathology Center at Duke University.

What Shannon is getting at is that biobanks are not currently required to be CLIA compliant the way labs are required to be. And they never have. Biobanks are unregulated, and many in the field argue standards, and therefore, biomedical research, is suffering as a result.

This is the second in a series of interviews on the topic of biospecimen quality, and today we focus solely on storage and the biobank.

Shannon is also the Vice Chair of the College of American Pathologists (CAP’s) Biorepository Accreditation Program, the country’s only program of its kind to offer such accreditation. This year CAP is celebrating their 50th anniversary of offering laboratory accreditation. They're widely seen as the leader in lab quality assurance.

Biobanking is a relatively new industry, it's true. Time Magazine made it one of their 10 ideas changing the world in 2009. So is it nigh on time for biobanks to come under one regulatory agency such as CMS and the CLIA program? Some international biobanks, many of which were built in Europe based originally on American models, now serve already as standards of excellence back here across the pond.

Has Shannon heard pushback from the community against coming under CLIA? Why are biobanks going for CAP accreditation in the first place?

What is the biggest issue for storing samples? Why do biobanks struggle with sustainability?

We come in at around 28 minutes.

Pharma Stepping Up, Footing the Bill for Genetic Testing & Counseling: Jordanna Mora, Alnylam

It seems to be human nature to value and pay up to hundreds of thousands of dollars for a little white pill that we can drop on the floor--and granted, can do wonders for us, but we want to pay nothing or very little to be told what is wrong with us so that we might know which little white pill to use in the first place.

So let's talk today about the The Alnylam Act, a program to shake up the business model in diagnostics and genetic testing on behalf of patients. The Alnylam Act is what it looks like when a drug company gets proactive and says, hey, we will step in and pay for patients to be genetically tested and counseled for the diseases on which we are working.

“We did this to reduce barriers to genetic testing—and the delays are often pretty long in rare diseases--so that individuals can make more informed decisions about their health.”

That’s today’s guest, Associate Director of Medical Affairs at Alnylam Pharmaceuticals, Jordanna Mora. And just to say it again, you understood her right. Her company, Alnylam, is paying for patients to be genetically tested and counseled.

Is Jordanna hearing any pushback over conflict of interest? After all, the patients who would be testing positive might be candidates for Alnylam’s drug.

The therapeutic we are talking about here is not on the market yet. In theory, it is set to be approved this August, and would be the first of the RNAi drugs. It will be an exciting day for the company, for patients, and for the drug development industry as a new class of treatments is born.

After years of seeing the diagnostics industry struggle to win reimbursement for their innovations, it's refreshing to hear about a drug company filling in the precision medicine gap for the good of patients, many who get misdiagnosed or wait way too long for a diagnosis. Will the Alnylam Act be a model for other drug companies?

“There are a number of companies doing very similar programs, and I think its fantastic,” says Jordanna.

We go for just over 15 min.

Are We Asking Too Much of Genomics in Cancer Research? Tony Letai, Dana Farber

It’s a question we’ve asked on the program before. Are we over relying on the genomics route getting us to biomedical research paradise? Should we be putting more eggs in other baskets?

After combing through lots of clinical trials data, Tony Letai of Dana Farber and the Broad, found that a majority of cancer patients have not benefited from precision medicine. On today’s show he says we need to rethink our approach to cancer research and treatment.

“I think we have a block in our minds in cancer biology about the rules--there are some rules we’re playing by that I don't think we need to play by. I think we can cheat,” he says.

Tony says one of these “unspoken” rules is that we need to use "initial conditions” got from a cancer cell that has been biopsied and killed and broken down for it’s parts, particularly for its “bag of DNA.” Today Tony advocates for an additional approach to genomics, the revival of an older tool, that of screening the live cancer cells against all available drugs. He calls this “functional precision medicine” or a combinational approach, and believes that in 10 years these functional assays will be standard of care in labs everywhere.

Recently we did a show with the CEO of Karius who is bringing sequencing to the world of infectious diseases. What Tony wants to do is bring more of the world of microbiology and cell culture from infectious disease over to the world of cancer treatment.

We have heard of others doing this, as Tony acknowledges. A couple years back we featured Krister Wennerberg from FIMM and last year a private company in Seattle doing something similar. Tony says he has founded a new society to provide network support for this new group called the SFPM or Society for Fuctional Precision Medicine. We finish up at 27 minutes.

A New Method for Long Reads: Hanlee Ji of Stanford on Cancer Genomics Tech 2018

Hanlee Ji is the Senior Associate Director of the Stanford Genome Technology Center as well as an oncologist at Stanford. He’s also a clinical geneticist. In other words, he doesn’t need to take off his glasses and spin around in a phone booth to be able to do about everything.

“I was in fellowship for a long time,” he says in todays interview.

Long reads have been an important theme in the genomics community of late, and Hanlee’s lab recently developed a new method for isolating long fragments of DNA that rivals the long reads of PacBio and Oxford Nanopore. The new method is the first we’ve featured that uses 10X Genomics’ linked reads. The new method also uses CRISPR and CATCH (a new sample prep system from Sage Science), and because it’s done with digital PCR, it offers the nice advantage of only requiring very small sample sizes.

Applications? Hanlee says he’s most excited to use it to identify 're-arrangements’ such as those in congenital disorders or oncogenic drivers.

Hanlee’s lab is also involved in a new clinical trial using precision cancer vaccines that is pulling him headlong into the immuno therapy space.

With a foot deep in the world of genomic technologies and another foot in the clinic, what does Hanlee the oncologist want to tell the technologists? And what does Hanlee the technologist want to tell his colleagues, the cancer docs?

It’s some big questions, and he takes around 27 min to get around them. Enjoy.

March 2018 in Genomics with Nathan & Laura: DTC BRCA and Revisiting All of Us

23andMe steals the headlines yet again.

“If somebody is worried about breast cancer susceptibility in their family, they should certainly not be using this test.”

That’s our monthly commentator and genetic counselor, Laura Hercher, talking about BRCA going DTC. But wait a minute. Then she says the test could be good in some instances.

Fellow commentator Nathan Pearson cracks us up with his new term for the NIH’s All of Us Research Program. We question the big science project after the New York Times reveals that several major institutions, including Geisinger and Kaiser, are pulling out.

It’s Nathan and Laura back to offer their inside take on the lead genomic stories of the past month.

And no matter what, we won’t mention 23andMe again next month. We hope.

Personalized Medicine in the Trump Era with Edward Abrahams

The Personalized Medicine Coalition advocates for a wide group of constituents, including scientists, health care providers, entrepreneurs, payers, and patients. Which is why we’ve often wondered how the organization can be absolutely clear in their priorities.

Today, PMC President Edward Abrahams joins us to answer that question.

For example, take the topic of laboratory developed tests. The country is currently experimenting with an anti-regulatory political direction. Is Ed happy that the FDA has dropped their guidance for LDT regulation? With such a disparate constituency, what does he think is the best way forward? What about the CMS announcement recently that there wouldn’t be any reimbursement for diagnostic tests that weren’t FDA approved (isn’t this at odds with anti-regulatory policies?)—does Ed have any insight here? Also, is the current boom in direct-to-consumer testing a boon or bane for the industry?

When Obama’s Precision Medicine Initiative was launched, many organizations which had been using “personalized medicine” in their nomenclature were pressured to change their names. Ed says he’s still happy with the old term and in fact is working in congress to create the first Personalized Medicine Caucus.

We come in at around 27 min today with one of those unique industry veterans who can talk science with scientists, can talk real with patients, and carries clout on The Hill.

Going Beyond the Liver with RNAi: Chris Anzalone of Arrowhead Pharma

Fifteen years ago, folks in the industry were buzzing about RNAi the way they talk about CRISPR today. Then things went quiet for the technology, at least in the news. Until last year.

In September of 2017, Alnylam Pharmaceuticals, the leader in the RNAi space, announced such positive phase III study results that most experts in the business expect an FDA approval soon. It will be the first for an RNAi drug.

So what took the technology so long, and what was the key to the great results? These are questions we ask today of Chris Anzalone, the CEO of Arrowhead Pharmaceuticals, another runner in the RNAi race. Arrowhead scooped up various RNAi programs from some of the big pharma giants, including Roche and Novartis, during the "quiet" years. Coupling these assets with some of their own technology, they are going after not just some of the esoteric diseases we've come to expect from a new platform first proving itself, but are also targeting the very recognizable Hepatitis B.

How does Arrowhead plan to further differentiate themselves from Alnylam?

“One of our great contributions to the field and, frankly, to world health, is our ability to bring this outside the liver,” says Chris.

So far, the major programs from RNAi companies like Alnylam are all limited to liver diseases. Arrowhead is the first to have drug candidates which go after non-liver diseases. It's a major step forward for this RNAi technology.

How we will know when RNAi has matured, we ask Chris at the end.



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