Biotech Strategy Blog

Commentary on Science, Innovation & New Products with a focus on Oncology, Hematology & Cancer Immunotherapy

Posts from the ‘Genomics’ category

Churchill College, Cambridge: Yesterday heralded the 4th and final day of the EACR Cancer Genomics conference with some invited speakers and proffered papers based on research from several groups and labs.

Churchill College, Cambridge

We got to see through the keyhole on several important areas of research that highlight both challenges and opportunities faced by the field.

The good news is that the opportunities provide insights into how we can learn from ongoing and optimise future clinical trials.

 

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Churchill College, Cambridge:  Yesterday, the main focus at the EACR Cancer Genomics conference was on immunology-related topics as they pertain to genomics.

A rainy day in the Fens for #CG17

Unfortunately, however, the Great British summer ended as almost as soon as it started – I can confirm that it started on a Wednesday this year and fizzled out by the following Tuesday!

Consider that on the first two days of the conference it was gloriously sunny and those wooden benches were full of scientists sitting outside eagerly discussing their research or various collaborations afoot.

A mere 24 hours later, the heavens opened and steadfastly drizzled all day long, much to the chagrin of the attendees.

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Cambridge: the third annual European Association for Cancer Research (EACR) conference on cancer genomics is underway at Churchill College in the UK. (Official Twitter hashtag: #CG17).

Churchill College, founded by the former Prime Minister, Sir Winston Churchill, is a short 15 minutes walk from the historic city centre and has an edgy modernist field to it, with thought provoking sculptures scattered throughout the grounds. It’s a far cry from the more romantic and dreamy spires of Oxford portrayed in the TV detective series, Morse and Lewis.

Despite all the interest in cancer immunotherapy and immuno-oncology, it’s important to remember that cancer remains a disease of the genome, which is why we decided to cover this meeting for the first time. It has an impressive line-up of keynote speakers, as well as researchers presenting posters.

All too often now on the cancer immunotherapy conference circuit, it’s the same thought leaders giving a repeat of their ‘party piece’ standard “keynote” talk so it’s refreshing to hear new voices who are at the leading edge of cancer research, albeit in a slightly different niche.

What we are starting to see is the convergence of cancer immunotherapy with genomics, and that was very evident in the posters that are directional of where the field is going. More on that later.

This is the first of three daily blogs that summarise some of the insights and take-home messages from the EACR Cancer Genomics conference at Churchill College, Cambridge.

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Following on from yesterday’s post on the potential for small basket trials in ER+ breast cancer with the ESR1 mutation, I wanted to highlight another area where these type of highly focused and rational studies appear to be not only useful but also potentially produce stunning responses.

Some of you will recall the fascinating and widely told story of a single bladder cancer patient at Memorial Sloan Kettering who was resistant to multiple lines of therapies. The team sequenced the genome and found a rare TSC1 mutation. Importantly, this is known from pediatric astrocytoma studies, to be sensitive to an mTOR inhibitor, everolimus (Afinitor). The refractory patient was given the drug and responded well. The rest is history, as they say.

Can we learn more from these type of appraches, i.e. genomic sequencing of patients who have relapsed after initial therapy?

Can we also learn more from the few exceptional responders in clinical trials – what was unique about their response that elicited such a stunning effect?

The short answer is a resounding yes – to learn more about some stunning new genomic approaches to research and the lessons we can learn for future drug development, sign in or sign up below.

Following on from yesterday’s update on how proteomics and genomics can help us make better decisions in breast cancer at the Miami Breast Cancer Conference (#MBCC14) organised by PER, today also looks at the complexity of genomics, but from a different lens – can genomics impact the way we actually treat patients?

Interestingly, last week there was a rumour (unconfirmed) that Dr Debu Tripathy (UCLA) was heading to MD Anderson to head up the breast cancer division following Gabriel Hortobaygi’s retirement. That move was confirmed yesterday, with a tweet from Dr Naoto Ueno, who is part of the group:

His talk on the increasing role of genomics in breast cancer on Friday was engaging, thoughtful and well delivered.

It also made me (and several others) stop and think.

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Foundation Medicine ($FMI) will be presenting on Jan 15th at the J.P. Morgan Annual Healthcare Conference, which we will be following remotely on the blog.

Yesterday, Foundation Medicine announced an extension to their agreement with Novartis to provide molecular information and genomic profiling for clinical oncology programs, extending the existing collaboration through September 2016. The agreement also includes an option for Novartis to extend the term for an additional two year period.

A number of readers have written to me over the last couple of months after noting my enthusiasm for this technological approach and asking – what’s so interesting about diagnostics and genomics or – will it become mainstream?

Just after the ASH 2013 annual meeting,  I had the privilege to interview Dr Vincent Miller, Chief Medical Officer of Foundation Medicine and discuss his perspectives on the genomic sequencing field and where they are going.

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There was so much good science on display at the recent 2012 annual meeting of the American Association for Cancer Research (AACR) in Chicago that any blog posts are but a personal snapshot or postcard.

Bill Sellers VP Global Head Oncology Novartis Institutes for BioMedical ResearchOne enduring image I have from the plenary presentation on “The Genetic Basis for Cancer Therapy” by Bill Sellers, VP/Global Head Oncology at Novartis Institutes for BioMedical Research was the video he showed of the robots that are used for automated cell profiling.

Imagine the advertisements that show robots being used to build cars, but now the robots are undertaking automated laboratory work in pursuit of new cancer compounds. Wow!

During his presentation, Sellers described how Novartis have built a robust preclinical translational infrastructure.

He went on to say that, “many experiments we have done in the past, and even many molecules that were put in the human, really were only profiled against a limited number of preclinical models such as one cell line.”

In order to make preclinical data more reproducible, Novartis had the goal to move from testing against one cell line to testing against an encyclopedia of cell lines.

This has now become a reality with the launch of the Cancer Cell Line Encyclopedia (CCLE) in collaboration with the Broad Institute. The CCLE was recently announced by Novartis in a media release, and details were published online on March 28, 2012 in a letter to “Nature” (doi:10.1038/nature11003).

The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity

As described in “Nature”:The Cancer Cell Line Encyclopedia (CCLE) is a compilation of gene expression, chromosomal copy number and massively parallel sequencing data from 947 human cancer cell lines.

When coupled with pharmacological profiles for 24 anticancer drugs across 479 of the cell lines, this collection allowed identification of genetic, lineage, and gene-expression-based predictors of drug sensitivity.

Sellers noted in his AACR plenary presentation that the key to using the CCLE is for profiling and to:

“identify subsets of cancer cell lines that are sensitive to a given therapeutic versus those that are not. And then better yet to identify the markers of sensitivity that are differentially expressed or present in the sensitive versus insensitive cell lines.”

Novartis Institute for Biomedical Research Automated Robotic Drug DiscoveryTo do this, Sellers described how Novartis have built a robotic system that e.g. automates cell profiling.  In approx 3 months with this system we can profile 600 cell lines for about 1500 compounds, he said.

This type of preclinical automation is speeding up cancer drug discovery through the ability to more rapidly identify those compounds that are associated with and have activity against different mutations.

In my view, this will drive innovation through the effective and efficient screening of potential new cancer compounds, with the result that only those compounds with demonstrable promise progress.

AACR have made Bill Sellers plenary presentation available as a free webcast from the 2012 annual meeting (along with several others).  I encourage anyone interested in how cancer biology is driving cancer drug development to watch this.

This weekend I will be at the annual meeting of The Association for Research in Vision and Ophthalmology (ARVO) in Fort Lauderdale.

I’m excited about attending because earlier in my career I worked at Alcon Laboratories on European IDE clinical trials for three novel intra-ocular lenses.

ARVO is the ophthalmology equivalent of AACR and is where scientists involved in drug, device research meet to discuss new findings and early stage research.

The title of meeting is “Visionary Genomics.”  After listening to the plenary session at the recent AACR annual meeting by Lynda Chin on how insights from cancer genomics are translating into personalized medicine, I’m looking forward to seeing the impact of genomics on vision research.

Sunday’s ARVO/Alcon keynote presentation is from Roderick McInnes who is the Canada Research Chair in Neurogenetics at McGill University in Montreal.

A presentation that is already generating some advance interest is Sunday’s presentation of the results from the Comparison of Age Related Macular Degeneration Treatments Trials (CATT).

Age related macular degeneration (AMD) is the leading cause of vision loss in those over 65 in the United States, with over 7 million people estimated to be at risk.  Once you have AMD in one eye, you have a 43% risk of developing it in the other eye over a  five year period, a scary statistic!

The first CATT clinical trial is between bevacizumab (Avastin®) and ranibizumab (Lucentis®), both similar anti-VEGF inhibitors that are derived from the same monoclonal antibody.  It will be interesting to see whether the data supports the current practice of off-label use of bevacizumab given its lower cost compared to ranibizumab.

The findings from this data will also potentially impact aflibercept (VEGF-Trap) that is being co-developed by Bayer and Regeneron.  In February, Regeneron submitted a biologics license application (BLA) to the FDA for the use of VEGF-Trap in wet AMD.

The initial results from the aflibercept phase III AMD trial announced late last year showed a non-inferiority to ranibizumab.  If aflibercept is approved and comes to market in 2012, depending on the CATT results, it may have to compete on price against off-label bevacizumab in AMD.  Whether a more convenient injection once every two months for VEGF-Trap (compared to monthly for Lucentis) is sufficient to justify a price premium, it will be interesting to watch the market dynamics in this space.

You can find more about the meeting on the ARVO conference website and they have also put up a blog for the meeting.   The theme of my blog posts over the next few days will be ophthalmology related, and I expect to be live tweeting from ARVO 2011 on Sunday and Monday.  I’ll also be aggregating tweets from the meeting (hashtag #ARVO11) on this blog.

 

This month is Parkinson’s awareness month.  Following on from my recent interview (that you can read here & here) with Dr Todd Sherer of The Michael J. Fox Foundation for Parkinson’s Research, I was interested to read about progress being made on the road to towards targeted therapies.

The April 2011 issue of Nature Chemical Biology reports the development of a selective inhibitor of leucine-rich repeat kinase 2 (LRRK2), a gene that is mutated in some patients with Parkinson’s disease.

The team of researchers from Dana-Farber Cancer Institute, Harvard Medical School, University of Dundee, Scripps Research Institute and ActivX Biosciences applied a novel, screening strategy focused on selectively inhibiting LRRK2.

The result was the identification of LRRK2-IN-1, a novel analog that inhibits both wild-type and mutant LRRK2 kinase activity. The team confirmed the activity of LRRK2-IN-1 using human lymphoblastoid cells from a Parkinson’s disease patient with the LRRK2 mutation.

Unfortunately, LRRK2-IN-1 was unable to cross the blood-brain barrier, which means that it is not suitable for Parkinson’s disease.  However, this research is progress on the road to LRRK2 inhibition and the development of a targeted therapy in the future.

Moving forwards Parkinsons’ researchers may wish to consider combining new small molecules with nanoparticles that are able to cross the blood-brain barrier; this may be the way to deliver targeted therapies to the brain.

 

ResearchBlogging.orgDeng, X., Dzamko, N., Prescott, A., Davies, P., Liu, Q., Yang, Q., Lee, J., Patricelli, M., Nomanbhoy, T., Alessi, D., & Gray, N. (2011). Characterization of a selective inhibitor of the Parkinson’s disease kinase LRRK2 Nature Chemical Biology, 7 (4), 203-205 DOI: 10.1038/nCHeMBIO.538

There are 5,396 posters at the 102nd Annual Meeting of the American Association for Cancer Research (AACR) here in Orlando. Intermingled with the exhibitors (something that no doubt encourages traffic to the exhibits), the posters provide a window into the world of current cancer research and the spirit of collaboration.

Researchers from all over the world present their latest scientific discoveries, what they may have spent 3 years or more years on while studying for a Ph.D or undertaking a post-doctoral fellowship.

The research is innovative, and what’s seen at AACR is often at the cutting edge and shown prior to publication in a major journal.

What is palpable is the energy surrounding the poster discussions as experts, thought leaders and leading researchers network and share ideas with typically more junior colleagues, and in the process relate their experience to the poster being presented.

In a world of fixed term grants, the poster session is also an opportunity to showcase research to those who may be looking to hire new talent to their team.

It takes six poster sessions over four days for the 5000+ posters to be presented. I’m looking forward to the exercise!

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