cancer


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?

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.

Does the Reproducibility Project in Cancer Biology Offer a Model for a New Kind of Science Auditing?

Here on the show, we’ve talked about the lack of reproducibility for much of biological research. We’ve bandied around various percentages--is it 50% or up to 90% that can't be replicated? And we’ve poked around various issues that may be causing such poor science.

Nicole Perfito is the manager of the Reproducibility Project: Cancer Biology, an effort between Science Exchange and the Center for Open Science. The goal of this project is to take nearly forty “high impact” papers in the field of cancer and try to replicate them.

The team has reproduced several studies already. What are the main issues that are coming up? How helpful are the original authors being? And are there some low hanging fruit which might lead to dramatic improvements to research if adopted?

The project is still underway, but already Nicole and her team have some interesting hunches.

Is This the Future of Clinical Trials for Cancer? Stanley Hamilton on the NCI’s New MATCH Trial

It’s taken some time, but the NCI is finally sponsoring a big time clinical trial for cancer where the patients are organized by the genomic pathway that defines their cancer rather than the organ type.

"Instead of being a breast cancer trial, or a colorectal cancer trial, or the usual construct that’s been used, this one is obtaining biopsy specimens from patients with a whole variety of differing tumor types, evaluating them with a standardized platform to identify abnormalities, and then linking those abnormalities to arms in the trial with drugs targeted to those abnormalities. This is a completely new way of doing a clinical trial and becomes an important step in moving forward a precision medicine cancer therapy approach,” says today's guest, Stanley Hamilton, head of Pathology and Laboratory Medicine at MD Anderson Cancer Center.

How are the four centers participating in the trial going about selecting patients for this new trial? And what pathways does Stanley foresee dominating the trial?

Stanley’s lab has chosen to use Thermo Fisher’s Ion sequencers to characterize the patients’ genomic pathways. Why? Find out the answer to these questions in today’s interview with one of the leading PI’s for this unique clinical trial.

Want Answers? Look to the Non-Coding Region of the Genome, Says Cancer Researcher, Tim Triche

Listen to Tim Triche from Children's Hospital Los Angeles for very long and you’ll get excited again about cancer research. I couldn’t stop listening. Which is why his interview is being published in two parts.

Now sure, like other guests we’ve had on the show, Tim calls this the “absolute golden age of biomedical research.” But Tim has a unique story. He has been, and is still - though less so now, he says - an outlier in cancer genomics. Whereas most cancer researchers talk about genes, Tim is more interested in non-coding RNA.

An avid user of microarrays, Tim begins Part 1 of the interview with a reference back to “a very interesting experiment” done at the Affymetrix research lab when the first arrays were being designed. The Affy research team put (nearly) the entire stretch of chromosome 21 onto a wafer, and in a “beautiful Science paper” showed the importance of the non-coding or inter-genic region of the genome.

Using the Affymetrix Exon array that was developed as a result of the experiment, Tim has continually demonstrated that there are indeed useful diagnostic and prognostic cancer biomarkers to be found in the non-coding RNA.

And speaking of technology from the early 2000’s, Tim argues that we should reconsider GWAS studies. Perhaps there are still some simple answers to be found when considering the whole genome and not just genes.

In Part 2, Tim vows the incredible staying power of the array technology in the clinic as well as research. He also responds to recent skepticism over whether the age of genomics is delivering on its promise.

Editor's Note:  In this interview, Tim refers to an older generation Affymetrix array (GeneChip(R) Exon 1.0 ST Array).  The newest array (GeneChip(R) Human Transcriptome Array 2.0) is able to measure gene and exon level expression of coding and long non-coding RNA with the ability to detect alternative splicing events.

Gene and Tonic: Competition for 23andMe, Four Tips for Attending AACR 2015, and "Swab Stories"

An Old New DTC Co. on the Move

Let’s start with a bit of trivia.  What company has resorted to selling genetic ancestry testing online direct to consumers?  Hint:  the company is located in the San Francisco Bay area, has banked more than 800,000 samples from customers all over the world, and is slowly transforming itself into major biomedical player.

That’s right.  You got it.  It’s Ancestry.com.   

This week, an article over at Fusion revealed a company on the move.  The CEO of Ancestry.com, Tim Sullivan, says the company is “exploring ways that we could participate in health and provide our users with health insights."  Ancestry.com--which was founded by a couple Brigham Young University Grads--has been gathering customers’ family history data for decades.  Now they realize the gold mine they’ve been sitting on is much bigger than scoring free passes to the Mormon temple.

Watch out 23andMe.  You’ve got competition.

Four Tips for Attending AACR in Philadelphia

Now, if you work in life science, no doubt you are either headed to or know someone that is headed to the biggest cancer research show of the year,  AACR 2015.  In about a week, 18,500 scientists, doctors, patients, business folks will  descend on Philadelphia to figure out how to get patients to survive cancer long enough to get Alzheimer’s.

For conference goers, we thought we’d offer some helpful hints for your stay in Philly.

First of all , if you’re from California, enjoy using all the water you want.  Go for it.   Stay in the shower for an hour.   Revel in the fact that you don’t have to order water at the restaurant table.

Second--and this tip comes from city leaders.  They ask, what scientist has time to go to a museum?  Here’s a hands on suggestion for duplicating an experiment by one of  America’s first great scientists.      You don’t even have to leave the conference building or your hotel.  Get hold of  a metal key--your room card won’t work--and plug it into any electrical socket.   City leaders are quoted as saying, “This is an easy way to feel what Benjamin Franklin felt as he discovered the conductive properties of electricity.  No driving through crowded city streets.  And any electrical outlet in the city will do.”

Third, if you do have time for a museum, we’ve found just the one for you: the Mutter Museum, a medical museum located in the city center.  

Here you will find:

-a malignant tumor removed from President Grover Cleveland’s hard palate

-a piece of tissue removed from the thorax of Abraham Lincoln’s assassin, John Wilkes Booth

-slides of Albert Einstein’s brain

-and our favorite,  a giant nine foot long human colon that contained over 40 pounds of fecal matter

Our suggestion for lunch:  the equally enticing Philly Cheesesteak.

Fourth, we suggest you skip the Liberty Bell.  It’s just not all it’s cracked up to be.

Swab Stories

Finally, last week we came up with 10 reasons to  have your genome sequenced.  To find out that you married your first cousin, we joked, or to have that sperm donation from college come back and haunt you in the form of  your own kid.  Well, it turns out these aren’t jokes.

Have you heard of the DNA truck?  This is a lab on wheels that has been going around New York City for five years now swabbing people’s cheeks to answer their most private genetic dilemmas.  Well, it was announced this week that the DNA truck will be the subject of a new reality TV series on VH1.  That’s right.  We can now watch as a woman finds out that last night’s date was with her brother.   The title of the show:  Swab Stories.  I’m not kidding.  The entrepreneur and soon to be star of the show, Jared Rosenthal, says, “DNA is a human need.  I hope people see that this is a lot more universal than they realized.”

Which leaves us with the question:  Who’s your daddy?

 

Knowing More about What We Don’t Know: John McPherson on Cancer Genomics

More than with any other major disease, the understanding and treatment of cancer is being transformed by genomics. And these are early days.

John McPherson has been involved in sequencing since the original Human Genome Project. He now directs the Genome Technologies Program at the Ontario Institute for Cancer Research. John chaired a panel on cancer genomics at the recent AGBT, or Advances in Genome Biology and Technology conference, and shares his thoughts on this year's meeting.

Like many others, John is excited about the new possibilities gained by long read sequencing, particularly in showing structural variations of various cancers.

We ask John which platforms he likes, and most importantly--in this day with increasing sequencing instrument options--how he decides how much to spend on sequencing to answer a specific question.

"Our goal is to be as accurate as we can," he says. "For single nucleotide variants (SNPs), we see about a 93-95% verification rate. And we’re pretty happy with that. The question becomes how many samples you do, and not what you do to a sample. Depending what question you’re asking, the number of samples affects your power overall.”

John works in Ontario. We ask him about the state of clinical genomics in Canada, a country with a single payer system.

Cancer Researcher at Mayo Says Illumina Platform Maxing Out, Looks to BGI/Complete

Today we bring you a story which you probably wouldn’t have heard at last week’s AGBT conference at Marcos Island. While PacBio and 10X Genomics were getting most of the buzz at the annual show on all things sequencing, it could be the new BGI/Complete Genomics platform that steals the show later this year, says David Smith, a cancer researcher at the Mayo Clinic.

In his research, David uses sequencing to analyze the connection between the human papillomavirus (HPV) with oropharyngeall cancer.

“A couple decades ago, the incidence of HPV in oropharyngeal cancer was less than 20%. And now at the Mayo Clinic, 80-90% of these cancers are HPV positive,” he says.

Why? A change in sexual practices, David says.

To find out just how HPV causes cancer and integrates into the genome, David is using ‘long read, mate pair’ sequencing. This is a new technology that essentially converts short reads got from such platforms as Illumina’s into long reads. David acknowledges the nice long reads coming from the PacBio machines, but says the cost is still prohibitive. He’s looking for a price that scales into the clinic, and for this, he's most excited about a product that BGI is rolling out later this year, i.e., an already assembled human genome sequencing for $1,000.

We finish the interview with a discussion about how well clinical genomics is being adopted into practice at Mayo.

Cancer 2014: The Year in Review with Anna Barker

Guest:

Anna Barker, Co-Director, Complex Adaptive Systems Center, ASU Bio and Contact Info

Listen (3:21) Andy's challenge

Listen (4:39) The year of immunotherapy

Listen (4:53) iSpy 2 and a new approach to clinical trials

Listen (6:42) The swan

Listen (6:35) A coalition of the willing

Listen (5:14) Six reasons biomarkers fail

In 2003, the then Director of the National Cancer Insitute, Andrew von Eschenbach, issued a challenge: “to eliminate the suffering and death from cancer, and to do so by 2015.”

Anna Barker is the former Deputy Director of the National Cancer Insitute, and she was at the meeting when Dr. von Eschenbach issued his challenge. Now at the end of 2014, we talk with Anna about the challenge and how far we have come. She offers her vote for the three most important developments in cancer this past year.

Who Do You Want to Hear From During the Holidays?

It's a tradition at Mendelspod to bring you unique shows that go off the beaten track at the end of each year. In the past, we've brought you interviews with a science historian, a science comedian, sci-fi writers, and futurists.

We're just planning our lineup for holiday season 2014, and we want your suggestions. On the list so far are a philosopher, a popular sci-fi writer, and the former Deputy Director of the NCI.

Make your suggestions here.

Thank you, Theral & Ayanna



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