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Personalized Medicine [Part 1] – The PROMISE...

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Cancer Research 101: Personalized Medicine [Part 1] – The PROMISE...

Monday, March 19, 2012

Personalized Medicine [Part 1] – The PROMISE...


Whether you call it personalized medicine, or precision medicine, or whatever, the promise of the $1000 (or less) genome has captured the imaginations and aspirations of the public and the research community alike.

This excitement is not ill-considered. One can assume that there are going to be vast improvements in our ability to prevent, diagnose, treat and cure cancers as we learn more and more about the mutations that drive the diseases.

As  Colin Hill contributed to Forbes on Feb 9, 2012 in his post “Beyond the $1000 Genome on the Forbes website.

“Larger availability of complete genomic data will have a profound near-term impact on cancer research. The ability to rapidly and economically sequence individual patient tumours will help us to better understand the biological mechanisms of cancer and will facilitate data-driven patient stratification. This, in turn, will facilitate more effective clinical trials and speed the development of new therapies.

The significant near-term growth of rich genomic data will impact the patient care side too. Companies ... will use this data to perform molecular analysis of tumours that will assist in pinpointing the optimal treatment strategies for individuals with cancer.”

But of course, no matter how cheaply it can be done, sequencing a single patient’s genome is not going to tell us much if we don't know what we are looking for. How will we know a “bad” mutation from a “neutral” mutation? As we saw with Craig Venter’s genome, his natural amount of genetic variability, and presumably yours and mine as well, is very high, and yet Craig Venter is by all accounts a healthy man.

Well, the supposition is that if we look at enough DNA sequences of enough cancer patients then a pattern will start to emerge and we will start to see certain mutations showing up over and over. How many will there be? Will some mutations be more directly linked to actual “causation” of the cancer (so called “driver” mutations) or will some be there as a consequence of the cancer and not actually involved in the origin or progression (so-called “passenger” mutations). Will we be able to tell the difference?

Answers to these crucial kinds of questions require a lot more data than we currently have. And that is where and how the International Cancer Genome Consortium (or ICGC) was formed.

Inaugural Meeting of Genome Scientists in Toronto 2007
Much like the Herculean world-wide effort to collaborate in determining the very first human reference genome sequence, the ICGC is also a massive consortium (website at http://icgc.org/) . The ICGC is a consortium not so much of scientists but of whole countries. The consortium was formed in 2008 after an inaugural meeting (Toronto) and report in 2007, to bring a global effort to bear in sequencing enough genomes for each of perhaps 50 or more types of important cancers so that we could start to answer some of the questions posed above. It is estimated that perhaps several hundred genome sequences derived from patients with any individual type of cancer may needed in order to be able to have statistical confidence of which mutations may indeed be the “drivers” vs. those that may simply be the “passengers”. If you consider the effort, and cost, of sequencing hundreds of genomes for each of perhaps 50 types of cancer, you start to see the enormity of the task, and why a consortium of countries in needed.

The ICGC is therefore funded in the main by governments and government agencies (federal and provincial here in Canada) of countries, along with some notable cancer charities and other funders. Each participating member country of the consortium is expected to invest at least $20 Million overall to that country’s activities. Furthermore, a commitment to fully, openly and quickly share ALL data with other qualified researchers world-wide is an absolute requirement for membership.

The secretariat of the ICGC is in Toronto, at the Ontario Institute for Cancer Research (OICR; http://oicr.on.ca), and Dr. Tom Hudson, an internationally renowned genomics researcher who is President and Scientific Director of the OICR heads the Executive.

OICR also operates the main data coordination centre for the consortium. Tom took me on a tour of the OICR server room about a year ago and I can tell you it is like something out of the movies :) The air conditioning costs alone for  just keeping the server room(s) cool must be enormous!

The goal of all of this of course is to have an international database of “signatures” of dozens of types of cancers, with enough confidence that we can start to use that data to better understand cancers at the gene and molecular levels, and be better able to determine predisposition to cancers (leading to better prevention strategies); to determine better and more pin-point diagnostic and marker mutations (leading to earlier diagnosis and better interventions), and to determine many new therapeutic targets for treating and curing more and more cancers.

In Canada, we have taken a leadership role for three different types of cancer – Pancreatic Cancer (ductal adenocarcinoma of the pancreas; collaborating and funding organizations can be found here; Brain Cancer (pediatric medulloblastoma; collaborating and funding organizations can be found here; and Prostate Cancer (adenocarcinoma of the prostate; collaborating and funding organizations can be found here.
 
Whether the ICGC actually achieves all of its lofty goals is of course yet to be fully seen. What is clear is that a major undertaking like this brings out what I consider to be the very best in science and scientists: the desire and willingness to not compete but instead to openly collaborate, to share data, and to work for the common good in ways that no single researcher or even a single country could manage.

This is so-called “big science” at its best and we should all be pleased that it is being undertaken in the international arena, and in the collegial and cooperative manner that it is.

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