cancer


Why Childhood Cancers Need Their Own Gene Panel: Tim Triche

When we first talked with Tim Triche of LA Children's Hospital, we found out he was a bit of an outlier among cancer researchers. He was an advocate for poking around in the non-coding RNA.

Today we welcome Tim back to the show to talk about a new gene panel that he has designed specifically for childhood cancers. It’s a first of its kind and was modeled quite closely on the gene panel for the NCI’s MATCH trial. The new panel has both a DNA and an RNA component, and the RNA side is by far the biggest.

"There are 1,400 different amplicons on this panel looking for RNA fusions. Thermo Fisher tells me it’s the most ambitious RNA panel that they’ve ever undertaken," Tim says in today's interview.

"When 100 cancer patients walk in your office, then 100 cancer patients walk in your office," says Tim, quoting a common line in the field that points to the uniqueness of every cancer.

Yet even though every cancer is different, certain biological commonalities combined with better sequencing tools is enabling the design of new gene panels to guide in diagnosis and treatment. More and more a cancer is looked at based on the drug that might treat it rather than the organ in which it grows. The new panel can guide this treatment.

Some of the most important targets on the panel are RNA fusion transcripts. What are they, and why are they so important for helping kids?

Childhood cancers come from inherited mutations, whereas most adult cancers have to do with the skin or the linings of the organs due to mutations caused by environmental impacts. Fusion transcripts are very common in the youth cancers and have been a big part of routine diagnostics.

If a mutation is there early in life, is it likely to turn into cancer sooner rather than later? Yes, says Tim.

“If you look at the incidence of childhood tumors, there’s a big bump in the first months or year or two of life, and then they disappear thereafter."

Additional benefits from these new next gen sequencing panels are that they can work with very small “real world” samples of tumor tissue, and they can also be used as discovery tools. Tim says the panel, called OncoKids, is ready to go for frontline therapy, and is hoping to get the word out to oncologists everywhere.

Thermo, Pfizer, and Novartis Pull Off a First for NGS in Lung Cancer

Today we get to bring you a feel good story, one of the major achievements so far in precision oncology. Three large companies—Thermo Fisher, Pfizer, and Novartis—put aside their differences to come together for patients.

The patients are those who suffer from non-small cell lung cancer. In June, the FDA approved for the first time an NGS panel with multiple genes for multiple drugs that treat this kind of cancer.

“It’s groundbreaking for patients, because instead of having to wait for a hierarchal testing approach to their cancer, this one test could be able to give the answer for the patient."

By hierarchical, Annie Martin, the VP Global Head of Precision Medicine at Novartis, means the usual stepwise approach to testing for patients with this cancer. Typically patients are tested for first EGFR, followed by ALK, followed by ROS1, followed by BRAF. Now, thanks to a new NGS panel out by Thermo, all of these tests will be done at once and has been approved for various therapies.

In addition to Annie, we’re also joined by Thermo’s Joydeep Goswami, President of Clinical Next Generation Sequencing and Oncology at Thermo Fisher and by Hakan Sakul, VP of Diagnostics at Pfizer to talk about their collaboration.

How did Thermo decide on this panel, and what possible future uses to do they see? And how did the three large corporations—one diagnostics and two pharmas--come together to pull this off?

Join us with three of the industry’s leaders as we uncover the work behind a major milestone for precision oncology.

Grail Merger, Genomic Autopsies, Overtreatment Alarm, and Controversy at Ancestry.com: May 2017 Review with Nathan and Laura

Is Grail already merging? Genomic autopsies? Does the House's new healthcare bill turn mere genetic risk into pre-conditions? Nathan and Laura are back to find meaning in the rush of May's headlines.

Laura cites a disturbing survey of over 2,000 women diagnosed with breast cancer that found half of them had unnecessary double mastectomies after genetic testing. She says unabashedly, “In big letters, it’s an ADVERTSIMENT FOR GENETIC COUNSELING.”

Speaking of alarms, Nathan says attorney Joel Winston’s blog against Ancestry.com’s terms and conditions was fear mongering.

We end with comments on the passing of one of the creators of the orphan drug industry, Henri Termeer.

Can You Name the World’s Largest Single Disease Research Charity?

Let’s take a break from the US and head over to the UK, home of the world’s largest single disease medical research charity.

Cancer Research UK (CRUK) raises five hundred million pounds a year for research and drug discovery into any and all of the two hundred plus types of cancer. The charity is extremely well integrated into U.K. culture, and uniquely English in that the donations are mostly small and come from all corners of society. A third of CRUK’s funding comes from donations averaging £10 or less.

Allan Jordan is head of chemistry for the drug discovery unit of CRUK. On today’s show he says that the democratic funding of the charity gives them a great deal of flexibility to do early stage drug discovery. Whereas a big pharma or biotech has to devote their resources to limited assets, or drugs, CRUK is able to spend more on basic biology research and follow the science into any type or cancer or multiple cancers.

There are very few conditions,” says Allan about his drug discovery unit in Manchester. "We don’t have to be specific about any particular disease area; we don’t have to be experts in one disease at the expense of all others. We can tap into that UK-wide expertise and network that can help us understand the biology.”

How is the charity working with the UK's national healthcare system? And does Allan hear the same kind of skepticism that we hear in the U.S. about precision medicine in oncology?

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.

Gene and Tonic: Excerpt of an Interview with Former President Obama in 2036

Interviewer: Congratulations on the Nobel. I mean the second one.

Obama: Thanks. I really feel like I earned this one for Physiology or Medicine. It took getting another doctorate degree, but I made it happen.

Interviewer: What I’d really like to know, Mr. President--looking back now, why did you do the whole become the president thingy?

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."

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."

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.

Cancer: Year in Review 2015 with Anna Barker

As we begin the countdown to the new year, we take a look back at 2015 in cancer research, treatment and prevention. Mendelspod is increasingly becoming known for the coverage of genomics and precision medicine, and cancer as a disease area offers a specific window whereby we can look at practical outcomes.

Anna Barker is the director of the National Biomarker Development Alliance (NBDA). Formerly the deputy director of the National Cancer Institute (NCI), she has worked on cancer her entire career and seen first hand the triumphs and setbacks. Last month at the National Press Club in Washington, D.C., Anna announced the creation of GBM-AGILE, a new kind of clinical trial for a very tough, rare cancer, glioblastoma multiforme. The project is the culmination of the work of Anna and many others to come up with a better system for validating biomarkers. This single trial is a global endeavor and already becoming a "movement" in cancer research with over a hundred and forty experts getting involved. Folks at the FDA are saying that GBM AGILE “raises the bar for clinical trials.”

Along with new ways of doing clinical trials, 2015 has also seen the explosion of new blood-based cancer tests known as liquid biopsies. Still mostly research projects, these tests will potentially offer patients a non-invasive alternative to expensive and painful solid tumor biopsies and offer the promise of someday improving cancer screening and prevention.

Immunotherapy drugs continued to dominate the list of FDA cancer drug approvals in 2015 with the first approval of an oncolytic virus therapy and the first approval of combination immunotherapy. In today’s interview, Anna reminds us that the recent breakthroughs in immunotherapy are the result of a 40 year journey. She goes on to question the herd mentality reflected in the over pursuit of certain targets.

Anna wraps up her review by pointing out the opportunity to go after rare cancers, such as GBM and some childhood cancers. She says the more common cancers such as the big epithelial cancers—breast and lung— are dauntingly complex with "gazillions of mutations.” But with rare cancers, “we can follow the genomic changes through to the cells, to the organs, and to the organism. I’m thinking that we should all begin to take a careful look at some of the rare cancers,” she concludes.



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