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Category Archives: personalised medicine

“Cracking Cancer” on CBC’s The Nature of Things tonight

Tonight’s episode of CBC documentary series The Nature of Things with David Suzuki features an in-depth look at the BC Cancer Agency’s Personalized Onco-Genomics (POG) project, which is exploring the feasibility of sequencing DNA and RNA from cancer cells to help physicians select the best treatment for each individual patient.

Project co-lead Dr. Janessa Laskin also did a great interview about POG on CBC Radio’s The Current yesterday.

I got to see a staff preview of the Nature of Things episode on Tuesday, and I think the production team did an amazing job at presenting a balanced view of this specific project and of cancer genomics in general. If you’re in Canada, check it out on the CBC tonight at 8pm! It’ll be repeated on Saturday, and available online at the link above.

NB I’m not directly involved with this project, but pretty much everything we do in my department (Canada’s Michael Smith Genome Sciences Centre) touches on POG in some way. Many of my colleagues and friends are featured in the documentary – it’s always very cool to see people you know on TV! We’re all very proud of the work we do; I hope you enjoy seeing inside our world!

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Quora activity for January 2015 – August 2016

Quora is a question-and-answer site. You can view all my contributions here; selected highlights are listed below. I encourage you to check out the other answers submitted for each question, too!

Cancer

Would it be possible to avoid cancer by modifying our DNA?

Is whole genome sequencing of any use in cancer diagnostics?

If our body can detect cancerous cells, why do people still get cancer? Does it mean that we can improve our body’s defenses against cancer before even getting sick?

If 2/3 of cancers are caused by chance mutations, why should I work to help prevent cancer?

Is it possible that cancer is not actually a disease to be “cured”, but it is actually an inherent defect of genetics?

Is cancer an intrinsic feature of life?

Is worrying about cancer the biggest cause of cancer?

What are the chances (if any), that a blind person getting cancer in the eye would allow them to see again?

What cure would be most beneficial to discover: HIV/AIDS or cancer?

Can Ebola be treated with cancer drugs?

Epigenetics

If two people have identical DNA fingerprints, what other molecular evidence does forensics use to distinguish between biological samples?

Can a methylation pattern be sequenced?

What could potentially be the most exciting application of epigenetic research?

Why hasn’t Lamarck been acknowledged in the face of the burgeoning advances made in the science of epigenetics?

In what way does histone methylation prevent transcription?

Is the epigenetic system of a person heritable?

Is there a meaningful way to diagnostically test a patient for epigenetic changes caused by long term use of medications?

Other Scientific Subjects

Is it a possibility that parents of genotype AA have an offspring with AS?

What is the reason that viruses are inactive when not inside any organism? What is the mechanism?

Will the final solution to HIV be to just accept it as part of the human genome?

What can you tell about a gene based on its tissue expression patterns?

What are some interesting examples of people becoming infected with typically fatal diseases (e.g. Ebola, HIV/AIDS, rabies, anthrax) through unusual means or at long odds?

Could cellular environment (pH, temperature, molecular crowding, redox state) affect a cell’s interactome?

What causes mutation in viruses?

Which (multicellular) animal is most deadly to humans?

What would happen if all the DNA in my body suddenly disappeared?

What are the most useful lab hacks, tips and tricks for molecular biology/biochemistry?

Do viruses have nutritional value for any organism?

What will next-generation sequencing be called a generation from now?

When will we be able to sequence the genome of every living vertebrate on Earth?

What are the oddest organisms?

Biochemistry: Why does the yeast two-hybrid system system have low specificity?

About Scientific Research and Careers

What does a principal investigator at a molecular biology lab spend time doing during the day?

How common is it for scientists to hire people to write their grant proposals?

How do I improve my grant writing?

I want to apply for a grant for a project, but I have no idea how to write a proper grant proposal. How can I go about this?

What is your favorite annual scientific conference?

Does a biochemist/biologist have to know all the reactions of cellular respiration or other general topics by heart after graduating?

Miscellaneous

Is there racism in Canada? Why?

What’s the best story about “fighting fire with fire”?

What are some of the best moments while taking exams?

Why do people believe in the ancient aliens theory?

If cloning of people was legal, whom would you choose and why?

What are some great optical illusions?

Which is the best way to pass the PMP exam?

Why do some people choose to use Quora over writing a blog?

 

The cancer genome in context: finding mutations is just the start

[Originally posted on Occam’s Corner at Guardian Science, in June 2013]

Sequencing the genomes of cancer cells lets us identify the mutations that drive the disease and develop drugs that target each mutation. But that’s just the start of the story…
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Nucleosome 1KX5 2
Cancer is caused by changes to the cell’s DNA – but there’s much more to a cancer cell than just its DNA. Image: Richard Wheeler/Zephyris
Cancer is a disease of the genome, initiated by mutations in the genes that usually control cell growth and division.Scientists started to identify the most common mutations found in the most common cancers back in the 1970s, although the limitations of the technology available at the time meant that progress was slow. Drugs that specifically target some of these mutations are already available and prolonging cancer patients’ lives. Now, new technologies such as whole-genome DNA sequencing allow us to identify mutations faster and more cost-effectively than ever before – mutations that are already feeding into the early stages of the drug development pipeline.

The first cancer to have every “letter” of its genome sequenced and every mutation recorded was a leukemia, in a study that was published in the journal Nature in 2008. Genomes of other cancers – lung, breast, melanoma – quickly followed, all also published in top-tier journals and heralded in the media as major breakthroughs. Now, just a few years later, the era of cancer genomics research is well established and single-genome studies are already old hat – it takes much larger studies these days, involving the analysis of dozens of cases, to attract the same kind of attention as the early studies. With the first wave of research behind us, several centres around the world are now starting to study how to incorporate genomics into clinical cancer diagnostics and treatment.

The power and the promise of genomics is that, given enough money, we can start to personalise the treatment given to each patient. For instance, imagine a hypothetical mutation already known to be present in 70% of, say, bone cancers. A targeted drug is developed that works well in that 70% of patients, but does nothing for the other 30%, and whose effects (or lack thereof) take weeks or even months to detect. Sequencing newly diagnosed bone tumours before choosing a treatment lets you give the drug to those who will benefit from it, and find another option for the other 30% without having to put them through weeks or months of futile treatment, complete with nasty side-effects. If you also routinely sequence other types of cancer, you might find that 5% of, say, liver tumours contain the same mutation, and can be successfully treated with a bone cancer drug that might not otherwise be offered to liver cancer patients.

If the history of cancer research and treatment has taught us one thing, however, it’s that things are never quite that simple.

Take the example of a mutation called BRAF(V600E), which is found in a number of cancers, including melanoma. A drug called vemurafenib that targets this mutation has been developed and works well against melanoma, a notoriously aggressive and hard-to-treat cancer. However, when the same drug was given to patients whose colon cancers also contained the BRAF(V600E) mutation, it didn’t work. This puzzle was solved last year by a team who discovered that colon cancer cells contain high levels of a protein called epidermal growth factor receptor that protects them from the effects of vemurafenib; melanoma cells don’t contain much of this protein, which explains the difference in response between these two tumour types.

Chalk this one up as a learning experience for a young field; we now know to look at mutations in the context of the other genes and proteins that are active in the whole cell, not as single entities.

There’s a lot of useful information still to be gleaned from cancer genomes, and – no doubt – a lot of other learning experiences in our future. But with lives on the line, can we find a way to learn these lessons sooner rather than later?

One intriguing option is to pair cancer genomics with a technique called xenografting, which involves inserting a small piece of a patient’s tumour into a mouse. The idea is that the patient’s tumour can be sequenced, promising-looking mutations identified, and candidate drugs (and combinations of drugs) tested against that patient’s tumour in a number of “avatar mice”. This approach can help doctors choose the right treatment for each patient much faster, and with less risk of subjecting them to potentially futile treatments and side-effects; it can also give us early warning of the kind of interplay between a gene mutation and its cellular context seen in the case of BRAF(V600E). As an added bonus, this kind of study – and it is very much in the early research phase at the moment, not part of standard clinical care – can also feed information and tissue samples back to research labs, to help with their work on drug resistance mechanisms and other aspects of the cancer genome in context.

It’s early days for the avatar mouse, a model that is not without its problems. From what I understand of xenografting, it’s as much art as science; some tumour types refuse to “take”, while others start growing immediately. It’s also highly likely that the mix of different cell types within the original human tumour changes during the process of implantation into a mouse, meaning that the transplanted tumour might not respond in the same way as the original. But work is under way, and it is going to teach us a lot.

We will need to explore more than one avenue of investigation to counter the manoeuvres of an ever-evolving enemy. Genomics is a powerful tool that is already helping us to make small advances. Considering the genome in context will take us even further.