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This past week, the Nobel Prizes in Physiology or Medicine was awarded to research scientists James Allison (University of Texas MD Anderson Cancer Center, TX, USA) and Tasuku Honjo (Kyoto University, Japan), each of whom has made an enormous contribution to the expanding world of immuno-oncology. Allison “discovered” CTLA-4; or more precisely, realized that blocking it could enable the body’s immune system to fight tumor cells, ultimately developing ipilimumab (Yervoy®) as a treatment for melanoma and, in combination, for several cancers. Similarly, Honjo discovered the PD-1 protein and launched the development of anti-PD-1 (and related anti-PD-L1) therapies that led to the rapid-fire approvals for pembrolizumab (Keytruda®) and nivolumab (Opdivo®).
Having listened to Allison speak a number of times, one thing that is almost ALWAYS pointed out is that these discoveries are simply the tip of the iceberg. His discovery of anti-CTLA-4 is a commercial success, and has made a significant impact on Stage IV melanoma patients, but it still has “only” increased 2-year survival from the single digits to almost 25%. Awesome stuff – but still, that means 3 out of 4 stage IV melanoma patients would still succumb to the disease in a couple of years.
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What Allison’s work has REALLY done is start the ball rolling in immunotherapy, which for a long time was relegated to little brother status in the cancer research world. His and Tasuku Honjo’s impact will be felt by more than the fraction of people who respond to ipilimumab, pembrolizumab, or nivolumab. They have opened the Pandora’s box of immune-related therapeutic options; it would be nearly impossible to tally the number of biotech startups and research initiatives that are enabled by the advances pioneered by these two men. Somewhere in there, a group of scientists are working on the next big breakthrough, one that wouldn’t happen without the persistence of Allison and Honjo.
That effect will be felt by the cancer patients that will be treated and, someday, cured by the advances in the field of immunotherapy. By scientists who aren’t even in college yet, treating patients who haven’t even been born. Groundbreaking means more than simply taking the first steps; it is laying the foundation of the building blocks to come. These building blocks offer the possibility of the impossible – enabling the body’s immune system to fight cancer and, down the line, other serious, chronic, or degenerative diseases.
This crowning achievement has a personal side to it. In this recent news clip, Allison’s realization of the human side of his discovery hits home, when talking about the first patient he ever met on ipilimumab. At the 4:50 mark, you hear James Allison say “we all started hugging and crying; before then it was all just numbers to me”. I don’t know that many patients, or even oncologists, truly appreciate the days, months, years, and even decades of research and work that go into scientific progress.
Behind every script and infusion and promising headline, there are dozens of scientists, hundreds of associated researchers, millions of dollars in capital, and countless careers dedicated to providing that single therapeutic treatment that will give someone a longer, better, or healthier life. And behind every US FDA approval, there are real people looking for that longer, better, healthier life. The work is not done, though. Even with the advances in immunotherapy, overall survival rates in melanoma hover in the 50–60% range at 2 years – a fantastic improvement in the past decade, but still not a cure for far too many. And while several cancer types respond to immunotherapy, it has not benefitted many others, notably having dismal results with breast cancer. Let’s rephrase – it has “not yet responded”.
To the cancer researchers who are working just as hard as Allison and Honjo toiled for years, the message from the patient side is an unequivocal “KEEP AT IT!” The reality is almost all of you will NOT win a Nobel Prize – sorry to be the downer. That shouldn’t be any kind of discouragement, but rather a realization that this award is recognizing the work of individuals that have set the scientific foundation on which to build for generations. As Aristotle once philosophized, “Dignity does not consist in possessing honors, but deserving them.” The field of cancer researchers collectively “won” this week with the announcement, and this should serve as a memorable and proud moment for all of you who contribute in some way to human health.
The work is not done, though. Even with the advances in immunotherapy, overall survival rates in melanoma hover in the 50–60% range at 2 years – a fantastic improvement in the past decade, but still not a cure for far too many. And while several cancer types respond to immunotherapy, it has not benefitted many others, notably having dismal results with breast cancer. Let’s rephrase – it has “not yet responded”. Notes Allison, “What we are working on now is understanding why it works and why it doesn’t… to increase the number of patients that benefit from this new type of therapy”. There are many, many patients out there looking for the hope this research is bringing, to give them the response that this subset of cancer patients has received. All is not lost, but there is also a long way to go.
Thank you, James Allison and Tasuku Honjo. As someone who has been on both anti-CTLA-4 and anti-PD-1 therapies on my way to a “malignant disease not suspected” radiology report, offering kudos on an award, no matter how prestigious, seems highly insufficient and inadequate. Your dedication, persistence, and life’s work have unlocked a door that will save so many from the ravages of cancer. The patients, their families, and the human population are indebted to your work. Enjoy an honor well-deserved, and thank you for inspiring the generations of cancer researchers and oncologists for years to come.
T.J. Sharpe is a Stage IV melanoma patient who shares his journey through cancer in the Patient #1 Blog on www.oncology-central.com, www.philly.com/patient1/, www.SkinCancer.net, and on www.NovartisOncology.com. He was diagnosed in August 2012 with melanoma tumors in multiple organs, only 4 weeks after his second child was born. Since then, he has undergone six surgeries and four immunotherapy treatments over two different clinical trials. The initial failures, and subsequent complete response, have been chronicled in his blog posts since December 2012. In addition to writing, he is a keynote speaker and consultant to the biopharma and clinical research industries, bringing an educated patient voice as a true stakeholder in challenging healthcare’s status and making a difference in patients’ lives via his company, Starfish Harbor LLC. A South Jersey native, T.J. lives in Fort Lauderdale, FL, with his wife Jennifer and two young children, Josie and Tommy.
Updated 30 January, 2019