Guest Column | June 10, 2016

Genome Sequencing - The Key To The Cancer Moonshot?

Genome Sequencing - The Key To The Cancer Moonshot?

By Ralf Huss, MD, Chief Medical Officer, Definiens

Though the announcement may seem recent, it was actually in October of last year when Vice President Biden boldly announced the “moonshot to cure cancer,” a personal passion fueled by his son’s death from the disease. Half a year later, this tall-order still has the industry – and world’s – attention, remaining the cause of consistent speculation and debate. With a recent invitation directed to nations around the globe encouraging involvement and contribution to the cause, it’s clear that the moonshot initiative is not losing momentum. Of course, to reach this goal, the initiative will need more than momentum – including the embrace of a breaking, advanced, holistic approach to research.

While both commitment and passion are certainly necessary components of the moonshot’s success, so too are efficiency and collaboration. Truly, to achieve this goal more than almost any other, it’s clear that the world’s sharpest minds will have to innovate like never before, within a new procedure that is fueled by rapid field research, cutting edge genetic analysis, great patient participation and even corporate healthcare compliance. To date, I have not witnessed a cancer vaccination success story (with an exception for vaccination strategies against cancers caused by viruses) but with each day, conference, clinical trial and industry report, we are closer to finding new ways to evaluate and engage with our current and future challenges.

Establishing A Strategy for Moonshot Success

All in all, the curing of cancer may be possible – although I can’t say that I am convinced it is something we can feasibly achieve in the very near future. The most immediate challenge I see ahead is the calibration of our understanding and view of cancer itself. While we have witnessed cancer spoken of almost as if it were one disease in the past, it’s worth revisiting and respecting the basic truth of a heterogeneous and sometimes even systemic disease. That is, cancers vary greatly and across a plethora of types. Because of this, there is no doubt about the long haul ahead, as the moonshot does not look to cure just one type or one cause of cancer. As such, this will require an advanced understanding of cancer biology along with the immune system and the available diagnostic tools.

One process that has been widely covered in the media and given grave importance is that of whole genome sequencing. Genome sequencing is a scientific process that provides a more detailed and thorough look at the tumor genome in order to allow more data to be gathered from said tumor cells. This valuable data could then be used by researchers and doctors in order to help in determining whether a patient, and by nature, their cancer, might be a candidate for today’s legacy and new to market treatments based on genetic testing and identified cancer mutations.

The American Association for Cancer Research believes that genome sequencing may be “rapidly transforming cancer research,” although, they note, leading insurers (i.e. Medicare) do not always pay for the procedure. In the media, the ability to collect more genome-sequenced data is commonly cited as immensely beneficial to the moonshot initiative. After all, it would allow researchers to implement a big data approach – the mere availability of more sequences would, naturally, allow more correlation studies. Without question, it would certainly take the initiative a step further. I believe this emphasis and benefit may be somewhat overstated. Genome sequencing is outstanding at doing one thing extremely well – but at no stage of the moonshot should we become too concerned with a certain one thing.

A Holistic Approach Through All “Omics”

In order to progress the cancer moonshot, the initiative must be viewed through the lens of all available “omics,” at the genesis and entirely throughout. This range of multiple molecular biology techniques and methodologies offers a combined, holistic approach to ensure all interactions of the cancer’s behavior are being monitored and considered, which can then be combined with genome sequencing and additional patient information. Simply obtaining knowledge of a cancer genome – in limited or vast quantities – will not progress us much further towards a sustainable cancer “cure.” That is to say, knowing of the mutations alone does not move the needle too much and there is a point in which the act of growing big data falls victim to the universal law of diminishing returns.

Even when treated and in remission, some cancers can commonly return within 6 to 12 months, and half of those patients with the identified mutation will now fail to respond to treatment. This tells us there is much more activity than a single mutation along the course of a cancer life span for directing our focus upon. This also aligns with words from George Church, the revolutionary geneticist who did call for increased genome sequencing years ago. Today, he is moving from an exclusive genome sequencing and DNA analysis orientation to one of a broader cancer tissue analysis, and he is even implementing a greater importance and focus upon the study of proteins; something he calls “panomics.” True to this thinking, it’s essential to plan and discuss the moonshot holistically – that is, the entire wave from sequencing all the way through to protein expression in the context of the cancer.

Incorporating Tissue Data and An Emphasis on the Immune System

What might the best practices and next steps for operating within “cancer panomics” be? Specifically, we need to move the conversation from genome sequencing and analysis to pursuing an understanding of how genetic signaling and messaging is altered by a cancer and its environment, as well as how it influences the entire biology of cancer from resistance pathways to the change of the local immune system’s response. This is precisely why we should be seeking a greater understanding of how the immune system operates in the context of the tumor setting. In respect to disease progression, we must seek to improve our understanding around its consequence and possible relapse after administering a selected treatment. From there, we can find hotspots and pivotal pathways for which vaccinations may help to specifically treat these events.

Furthermore, it is essential to place an emphasis on a combined data approach through the implementation of tissue and panomics data. Tissue is quite simply the ultimate expression of what’s going on in the body of the cancer. It describes how the cancer looks and how the cancer behaves in its environment. Something that has been described by pathologists for decades. But it also provides valuable data and a greater understanding of the immune system’s response. When we know the spatial resolution of cancer cells, encountering the complexity of the immune system, it provides a greater comprehension also around activity on a molecular level. My final recommendation is to take special note of a patient’s immune status prior to any type of treatment and to remain cognizant of it during the course of the treatment. Vaccination strategies require heavy involvement of the immune system, and require cells that present the antigen to said immune system, which can provide further valuable cause and effect learnings.

I believe understanding these outlined prerequisites for an effective cancer strategy is essential. A missing piece could cause insufficient or inadequate vaccination, which could have lack of affects for any patient or pursuit of a cure. Above all, researchers must remember to operate with a holistic toolkit and perspective, bringing both sides of the coin to the table. One side may be the vaccination against the tumor and changes within the tissue. The other side then requires us to understand and supplement the necessary components of the immune system. By marrying these sometimes distinct sides of the coin, we’ll invite an entirely new era of vaccination strategies, and this will advance not only the treatment of today’s patient, but the achievement of the moonshot initiative’s bold goal.