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Precision Medicine and the Paradigm Shift In The Development of Novel Cancer Therapies

Precision Medicine and the Paradigm Shift In The Development of Novel Cancer Therapies

By: Sarah Massey, M.Sc.

Posted on: in Blogs | Life Science Blogs

At the start of the year in his State of the Union Address, US President, Barrack Obama announced the launch of the Precision Medicine Initiative – a $215 million dollar plan to improve the current state of cancer diagnosis and stimulate the development of oncological therapies for specific types of the disease. This follows the reclassification of cancer as a disease of the genome; a decision made in recent years, following completion of the Human Genome Project.

Traditional cancer therapies have treated the disease on an organ-by-organ basis, categorizing the illness by the site of the primary tumor, such as the lung, breast or brain. The Precision Medicine Initiative points to a more individualized way to treat cancer based on the underlying genetic aberrations at its core.

So how will the Precision Medicine Initiative affect cancer diagnosis and patient treatment options? According to the National Cancer Institute in the US, it’s focusing its efforts towards personalized medicine in four main areas:

  • Expanding precision medicine clinical trials in an effort to match the patient to the right therapy. While the National Cancer Institute has already begun a number of these trials, they hope to build upon the idea of personalized medicine in order to determine the best treatment for a specific genetic mutation, regardless of the site of the initial tumor.
  • Overcoming drug resistance by studying how tumors that once responded to treatment have built up a resistance to a drug, and continue to proliferate. This goal ties into the next part of the National Cancer Institute’s plan.
  • Developing new laboratory methods for research to better understand an individual patient’s tumor characteristics, and how those cells may respond to a specific treatment. The National Cancer Institute says this will involve increasing the number of patient-derived tumor xenografts, as well as other 2-D and 3-D human cell culture models used to study the disease biology.
  • Developing a national cancer knowledge system which would allow physicians to predict patient outcomes based on a wide variety of data available for a particular cancer type. The database would include genomic information about the tumor, which would also aid researchers and drug developers in the creation of novel, individualized therapies.

To further understand how the paradigm shift in cancer research, diagnosis and treatment will affect how drugs are developed and clinical trials are conducted in Canada, I spoke to Dr. Sian Bevan, director of research for the Canadian Cancer Society. Bevan has been with the Canadian Cancer Society for 6 years, and has a background in medical biophysics. Her previous role was as the team lead for research programs with the Ontario Genomics Institute.

How is Obama’s Precision Medicine Initiative affecting cancer care in Canada?

There’s no doubt that precision medicine is a topic and an area of research that is of high priority among different countries. There is a lot of activity that is happening in Canada. It’s a broad theme about looking at medicine in terms of differences between people and differences in diseases, and that’s an area of research that Canadians have been working on for a long time. I think [the Precision Medicine Initiative] is formalizing some of that, and putting some new structures around some of that activity.
How will the shift from general to personalized cancer therapies affect drug developers?

It’s important to remember that the idea of precision medicine isn’t brand new. There’s certainly an evolution and new tools have been developed that are really accelerating the pace of some of this. There are a lot of different examples of drugs in cancer that are now standard practice that you would put in the category of precision medicine. For example, Herceptin is a drug that you give to women with breast cancer who overexpress a particular protein, so that in and of itself is personalized medicine.

The genetics and genomics and all of these different ‘-omics’ technologies in particular, are certainly teaching us more and more about different diseases and cancers. There’s far more opportunity to be more and more precise with respect to the treatments that we’re giving patients to ensure that we’re only giving treatment to people we know will respond, and avoiding the side effects for people who are not likely to respond.

Will classifying cancers based on the underlying genetic cause, as opposed to by the organ of origin affect the cost of cancer treatment?

In cancer, we typically talk about cancer diagnoses according to the part of the body where the cancer is found. There’s discussion about changing how we diagnose some cancers – instead of diagnosing by body part you could essentially look at tumors based on their genetic signature, and see different treatments that work for that particular type of cancer.

The challenge is that as treatments become more and more individualized you’re developing treatments that will be working, in theory, for a fewer number of people. You would be treating those people more effectively and sparing people who won’t benefit from that treatment, however the likely result is that it will increase the cost of caring for people with cancer and other diseases.

How will precision medicine affect clinical trials for novel cancer therapies?

In terms of clinical trials, to see whether a drug does or doesn’t work in a particular population of people is one important question to answer. The challenge is that that population of people – even though you have set criteria that you’re looking at and there’s always different inclusion criteria in clinical trials – will be different and will have underlying differences that precision medicine can help identify.

Is human genome sequencing inexpensive enough to allow for individualized cancer diagnosis and treatment? Does this approach make more sense for some types of cancers with extensive genetic variability, as opposed to others?

Whole genome sequencing prices have gone down – the notional goal is a $1000 genome. There are tests, for example the Oncotype DX® for breast cancer, which are paid for in certain circumstances, to help assess the likelihood of a breast cancer recurrence and how it responds to treatment.

The biggest challenge we have right now is not only paying for the genome sequencing itself, but understanding what it all means. It really speaks to fundamental, basic biology research which is a huge strength in Canada. It’s one thing to understand what the gene sequence is in terms of the combination of four particular letters (base pairs), but it’s equally important – or more important – to understand what changes in those sequences mean. There are some sequences in our DNA that if they get changed they’re more or less non-consequential – there are others that are critical.

There are also challenges in terms of the huge amount of data – even in just the human genome. One of the things that Obama’s Precision Medicine Initiative touches on is, how do we leverage what’s happening not just in a particular institution, city, province or country, but how do we look internationally at all of this information and this rich data. How do we put all that together to understand this better?

There are a lot of questions around that in terms of data privacy, ethics and patient and public engagement in research. There is a global initiative – Global Alliance for Genomics and Health – that is being partly led out of the Ontario Institute for Cancer Research. The Global Alliance is really focusing a lot on those big picture issues around international data sharing, and leveraging expertise in genomics across the world.

The funds that the [Canadian Cancer] Society is able to invest in research are donor-derived funds, so we significantly rely on the Canadian public to support the research across the country. Precision medicine is an area of increased interest, and something that the Canadian Cancer Society is very proud to invest in and promote activity in Canada, and around the world.

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This week the NCIC Clinical Trials Group (NCIC CTG) – supported by the Canadian Cancer Society – announced its partnership with Contextual Genomics, to study the genetic basis of cancer. Contextual Genomics is a developer of cancer tests that are genomics-based, and the company’s diagnostic tools will be used by NCIC CTG in current Phase 2 clinical trials.

How is the Precision Medicine Initiative affecting the way you conduct clinical trials? Do you think the shift towards personalized medicine will change the way cancer therapies are developed? Share your opinion in the comment section below!


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