Proteogenomics in cancer research

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Published: 4 Jul 2017
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Dr Henry Rodriguez - National Cancer Institute (NIH), Bethesda, USA

Dr Rodriguez speaks with ecancer at WIN 2017 about the translation of the proteins expressed in a patient's tumour into a map for druggable targets.

He highlights aspects of the Beau Biden Cancer Moonshot initiative, working with the National Cancer Institute, which aim to open global access to data libraries of tumour genomics and proteomics, including the APOLLO program and the International Cancer Proteogenome Consortium.

 

Today’s presentation is actually quite exciting. It’s something that we’ve been now working on actually for the past ten years at the National Cancer Institute. It’s a belief where we’ve been moving and you see now in oncology the field of genomics making great strides but over time as the technology now is starting to catch up and I believe it has caught up, which is a measure of the actual proteins which is what our drugs do target. Our belief is by combining the genomics knowledge now with this next generation proteomics technologies collectively you’re actually able to get a better representation of the underlying biology of the cancer itself and, more importantly, hopefully relate it back to your patient.

How does genomics turn into transcriptomics and into proteomics?

The easy way of looking at it is when people always go to school and they refer to as the central dogma. You have the piece of DNA, you can view the DNA as the blueprint of all the molecular underpinnings that surround our cancer biology. Ultimately that will be converted into this middle ground which is referred to as the RNA. This is essentially your transcriptomics. Ultimately that’s going to go into a protein which is the actual workhorse that carries all the functions inside a cell.

Does this come together in the APOLLO programme?

The APOLLO programme is actually one of the initiatives that we’ve actually moved forward which is an outgrowth of a large initiative from the cancer institute. So at the NCI what we’ve been doing for the past ten years and now in the next five years is a programme that’s affectionately referred to as CPTAC. CPTAC is the one that actually started this whole underpinning. We first moved in trying to understand the analytics of proteomic based technologies, once you understood those analytics then we actually wanted to apply it to biology. So we went after samples that were comprehensively characterised by TCJ genomically. Over the past year that caught the eye of our administration at the United States and in working with the Beau Biden Cancer Moonshot effort two programmes we’ve launched. One of them was the one that you just referred to as APOLLO which is a partnership amongst three organisations within the federal government: the Department of Defense, the Veterans Administration and the National Institute of Health. The other one that we’ve actually launched is this just incredible international effort that’s now referred to the International Cancer Proteogenome Consortium that involves greater than ten countries at this point, all with the belief of combining those two omics, genomics with proteomics. The best part is they’ve all signed a data sharing pledge which essentially means all the data that they generate genomically and proteomically they’re going to give it away to the public in general upon completion of their studies.

What is the future for this?

I’d say first and foremost ultimately what I want to see is better care towards patients. But if I had to put a timeline behind it I’d say we have to take it from a step by step process. So while genomics is at least ten years ahead, at least from my perspective, in terms of patient care, immediate actionable items to the patient, clearly proteomics is going to be a very complementary piece to it. So in my perspective from the NCI, what they’re doing is actually quite nice, they’re actually going to be now taking actual ongoing clinical trials, typically genomically driven. One of the things that we’re recognising is while we could develop panels for a prognosticative purpose, we’re really having a difficult time trying to understand how those patients actually respond to those treatment arms. So as a way of trying to better understand the biology and develop better predictive markers our belief is by combining genomics with proteomics, first and foremost, over the next five years we’ll get a better understanding of the cancer biology. That’s where I see a lot of these target-based assays really making its penetration, not just towards basic biology but beginning to understand the added value we could bring towards clinical trials themselves. Over those next five years, then in the post of that, I do see an area where we’ll be able to combine genomic panels with proteomic panels and hopefully collectively bringing information back to the tumour board and potentially back to the patient itself.

Do you see the proteomics you’re working with feeding into current systems?

Quite frankly I see them all as important. At the end of the day what’s key is the ones that you talked about, accessibility, all those clearly are needs that we need to do and address today. But the reality is there’s a lot of the underlying biology and oncology we don’t understand. That takes time and that takes investment but what we do understand today is that if you combine these two omic based technologies which today analytically, quantitatively and reproducibly both have caught up, the question I would give back to the people is if you could do it now and better understand the biology down the road why would you not? I don’t think there’s really an answer for that but the answer is yes, let’s move forward with it. I think that’s the spirit that I would see off that Cancer Moonshot effort.