cancer genomics


Precision Oncology at the Community Level with Lee Schwartzberg

When Lee Schwartzberg did his training as an oncologist some thirty years ago at Memorial Sloan Kettering in New York, he had a dream. And after training, he set off to make that dream a reality: to bring the resources, expertise, and research that one enjoys at a major research hospital cancer center to the community level.

This landed him at the West Cancer Center in Tennessee where he was made Medical Director and also Chief of the Division of Hematology/Oncology at the University of Tennessee's Health Science Center. And two years ago, after serving on various boards and founding a couple journals, he was finally appointed Chief Medical Officer of a national parntership of community oncologists that includes practices across the country from the East Coast to the West called OneOncology. He is now living out his dream.

Today he talks to us about how well precision oncology has made it to the community clinics. Lee says we are moving beyond the debate over molecular and genomic profiling. It's not a matter of whether, but when and which tests to include in the panels. He says, in general these days, physicians--and patients-- would like to see more information, as soon as possible after diagnosis.

"Our current recommendation at OneOncology is to order profiling (comprehensive genomic profiling) at diagnoses of advanced disease across cancer types," he says.

Is Lee in favor of population screening for the three major mutations, BRCA, Lynch, and FH? And what does he think of the trend of consumer-initiated testing?

It's a great chance to hear from one whose lifelong mission has been to take precision oncology out to the communities of America.

A Liquid Biopsy Technology that Doesn't Degrade the Sample: Raj Krishnan of Biological Dynamics

Raj Krishnan has a good story, and probably a good product. More data will tell. He's the CEO of Biological Dynamics, a new liquid biopsy company that is able to detect biomarkers in not only blood but other biological fluids. And the company's products are good for not only cancer but Alzheimer's and other disease areas as well.

Raj comes to precision medicine from electrical engineering. You don't hear that very often. One day in his lab while working on his PhD he had a classic eureka! moment. That unexpected discovery for which every scientist longs.

"The vast majority of methods for isolating biomarkers are either chemical or mechanical. Very few are electrical. And as an electrical engineer, I stumbled upon this methodology. At the time I was originally working on this, it was thought to be theoretically impossible. Late one night I came upon the answer."

The important thing about Biological Dynamics' technology, called ACE, is that it is able to draw the biomarker out of the sample without disturbing the biology. It is able to leave it in what Raj refers to as the "native state."

"Take a look at any Qiagen kit workflow or magnetic bead workflow and you can see 400 steps of which you have: destroy this, capture this, run this. How do you know fragmentation isn't being done by what you're doing to isolate the biomarker, as opposed to what it was in its native state?"

We have spatial biology. Should we call this native state biology?

Mapping Intracellular Context: Garry Nolan on Spatial Biology

First it was all about biomarkers. Then panels of biomarkers. But biology is complicated. Why does one patient respond to an immuno therapy when another which shares the same biomarker does not?

Welcome to the age of spatial biology.

Garry Nolan joins us today. He's a professor in the Department of Pathology at Stanford who's career has been a journey of seeing intracellular happenings more and more in context. Check out this cool analogy from a new paper his lab put out in Cell.

"The tumor micro environment (TME) is like a city composed of neighborhoods (e.g., industrial, residential, or agricultural), which are regions where specific functions of the city occur. These neighborhoods are distinguished by their composition of buildings, activities, and people, but they exhibit behavior of their own, such as industrial output or energy consumption. At a more granular level, people (e.g., teachers, doctors, and construction workers) play integral roles in the city’s function. The same concept applies when studying tissue.”

Today Garry walks us through the transition over the years from biomarker to spatial biology. He then discusses the Cell paper demonstrating that for the first time his lab is seeing that some "neighborhoods" react differently than others in the tumor micro environment. What will this mean in the clinic for patient treatment?

The technology making this possible is the CODEX platform, one of several developed in Garry's lab over the years. He tells of its conception and anticipates how it might evolve in the future.

We Can See Tumor Heterogeneity. Now What? We Ask Cathy Smith, UCSF

Cathy Smith counts herself among the Gleevec Generation after the landmark targeted cancer therapy. She’s an optimist who believes in the possibilities of precision medicine.

“We are outsmarting cancer,” she says.

Cathy is an Assistant Professor of Hematology/Oncology at UCSF where she is also an MD treating patients. Her area of expertise is in acute myeloid leukemia or AML. She joins us today to discuss a recent group paper and collaboration using new technology to track and monitor cancer evolution at the single cell level.

“It’s not that we didn’t know that this heterogeneity was under the surface, it’s just been hard to get at before we had this technology.” She is talking about single cell technology made by Mission Bio, a company based in South San Francisco.

As she looks forward to creating a first ever clinical trial using single cell data, Cathy says there are very hard questions to answer. It’s not totally clear what treatment decisions should be made when answer A comes back vs answer B. Still, she is optimistic that she and her colleagues will begin to find more answers for their patients.

“You don’t go into oncology if you’re a pessimist. You have to have hope that you’re going to get ahead of it. And the first step is to know what is going on."

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?

Meet Christian, Janos, and the New World of 3D Oncology

Today we engage in a rare discussion between a startup founder who is going beyond sequencing and working directly with cancer patient cells in 3D cultures and with one of his customers, the husband of a cancer patient.

Meet Christian Regenbrecht, the CEO of CPO or Cellular Phenomics and Oncology based in Berlin, Germany and Janos Flosser, a fund manager who invests in technology from Copenhagen, Denmark.

Today’s show is not only special for the fact that we have a researcher/entrepreneur sitting down directly with a patient for the interview, but also for a bold new approach to cancer genomics. Christian is not shy with his attitude about how we must shift our thinking toward oncology.

“Sequencing alone has proved remarkably unhelpful. And the belief that sequencing your DNA is going to extend your life is a cruel illusion,” says Christian at the outset of the interview.

So just what is Christian up to at CPO? How did Janos, a fund manager in another country, find Christian? And is this the new face of cancer treatment?

Has Computational Modeling for Cancer Genomics "Arrived?" with Shirley Liu, Dana Farber

It’s the question of the moment Are we living in the age of AI? Or is it still just hype?

When it comes to the latest research in immuno therapy, computational modeling is helping to answer key open questions, such as which patients might respond to which drugs.

"If you were to ask me last year about deep learning, I would probably say, aaah, most of the algorithms that are published are not really answering the important questions yet. But I think this year I am converted. We are starting to use deep learning, and we are starting to see interesting results.”

Shirley Liu is a Professor of Biostatistics at Harvard and the Co-Director of the Center for Functional Cancer Epigenetics at the Dana Farber Cancer Institute. Her lab has very recently put out three algorithms, TRUST, TIMER, and TIDE which represent some very exciting ways that bioinformatics is empowering not only cancer research but treatment decisions.

As a computational biologist, Shirley has found herself highly in demand today as the latest genomic tools such as single cell sequencing generate new amounts of data and as public databases such as TCGA make their rich cohorts available.

In today’s interview, she details these three new algorithms and makes the case that computational modeling has arrived for cancer genomics.

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.

Genetic Testing is Dead, Long Live Genetic Testing: Sean George of Invitae

A few years ago they were the new kid on the block, and now they are a leader of mainstream genetic testing. Last year their revenue and profit were significantly up.

And yet in today’s interview, CEO Sean George does not sound like someone sitting back on his laurels. In fact, he says his business model has got to change.

We expected Sean to push back against the recent approval of 23andMe’s direct-to-consumer BRCA test and the recent boldness of the DTC space in general, but he surprised us with a welcoming attitude toward his “coopetition.” He says that the DTC companies are providing general education in genetics to the public.

“It’s tailwind for us.”

When asked if they would ever consider going direct to consumer, Sean said that Invitae has already been piloting a broad comprehensive genetic profile for healthy people and has plans to launch it to the general public in the future. All of their tests, he emphasizes however, must be ordered through physicians.

Sean goes on to lay out his vision for the business model of the future.

"The model of single $3,000-$5,000 tests is clearly dead. It does not work. The companies do not scale. The value is there. It’s disappointing to me that it doesn’t work. But people are not paying for it. So our view is you've got to go at it the other way. Let’s unlock it. Let’s make it a utility in healthcare.”

April 2018 with Nathan and Laura: Golden State Killer and the Cancer Prediction Space

After decades on the loose, it’s cool the cops finally caught him. But is it cool how they caught him?

Nathan Pearson and Laura Hercher are back for April’s headlines. AACR had some more good news about Keytruda, and we take a look at the cancer prediction space.

DNA Day, the first cannabis based therapy to be recommended for FDA approval, the Zuckerberg hearing—there’s lots in here today.



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