May 30, 2017 / All Stories

Striving to Outsmart Cancer Together

Dr. Tom Hudson, a pioneer in mapping the human genome, discusses how understanding genetics may hold the key to breakthroughs for cancer patients.

Tom Hudson, M.D., vice president, oncology discovery and early development, AbbVie

Utilizing Biomarkers and Precision Medicine to Improve Cancer Care

by Tom Hudson

Historically, the treatment of cancer has focused on a "one-size-fits-all-approach," which can be successful for some patients but not for others. Chemotherapy and radiation, the standard of care approach for most patients living with cancer, can offer powerful responses, but are often associated with toxicity some patients cannot tolerate.

More and more, researchers are driven to look to specific genetic mutations and other molecular abnormalities in an individual’s tumor to identify, target and develop treatments for many types of cancers – something I continue to investigate since my time working on the Human Genome Project.

What began as a quest in 1990 to sequence all 3 billion letters in the genes and chromosomes of the human species – together known as the genome – continues to this day. This groundbreaking research has provided us with more than 2,000 genetic tests for human conditions.

Part of my involvement in this undertaking was bringing together successful multi-disciplinary research teams from dozens of institutional from different countries in Asia, Australia, Europe and the Americas, and strengthening the interactions between discovery teams and clinical researchers. This enabled us to benefit from new technologies and biology, make new discoveries, and accelerate the development of new, targeted cancer treatments.

We now recognize that cancers are fundamentally diseases of the genome and that understanding cancer begins by identifying the abnormal genes and proteins present in an individual’s tumor. This could include the 17p deletion and TP53 genetic mutations, which can be found in tumors from patients who have relapsed or refractory chronic lymphocytic leukemia and generally are associated with poor clinical outcomes. Other examples include as epidermal growth factor receptor (EGFR) mutations and amplifications present in solid tumors such as non-small cell lung cancer and glioblastoma. Identifying and analyzing these abnormalities will define how we diagnose cancer, determine how and when we develop and use targeted therapies to treat it, and shape the strategies that may hold the key to prevent the disease.

At AbbVie, we’re developing medicines tailored to the specific characteristics of an individual’s tumor genome to specifically target the changes inside cells which cause them to become cancerous, including the failure of programmed cell death or apoptosis. Unlike standard chemotherapy drugs, which work by attacking both cancer cells and healthy cells, these drugs attack one or more specific targets on or in cancer cells.

What’s equally important is the development of new diagnostic and monitoring tools. These can help accelerate the treatment decision-making process by identifying which patients are most likely to respond to targeted medicines, therefore potentially improving their chance of survival.

With the rapid speed of advances in research and our understanding of the biology of cancer, we are in a pivotal period for cancer care. As a researcher who has been battling the science of cancer for more than 25 years, I have never been more optimistic about the transformative therapies we are going to be able to deliver to cancer patients. The possibility of conquering cancer is what motivates me and my fellow researchers every day.

There was 10 years of work when most of the population started hearing about the Human Genome Project. Only when Jurassic Park came out, then people started understanding the genome.
So, I joined the Human Genome Project as a post-doc in 1990 at MIT. There had been two or three years of a lot of controversy in the scientific literature whether it would be helpful to sequence the genome. That’s what I was known for — mapping the physical map of the human genome …. “Gen” from gene and “ome” from chromosome. It’s that information in our genes and chromosomes that we inherit from our parents that we give to our children that can be abnormal in some diseases.
Most of the science is still, right now, being applied more to finding ways to treat cancer when you detect it. Then we started thinking, how can we actually start using those drugs at an earlier setting? It’s a concept that’s been studied a lot in human genetics … when you can identify someone’s at risk, when do you actually do the test? And we try to have some concept in medicine called “when you can actually do something about it.”
For example, if I knew I had a gene for Alzheimer’s disease, but there’s nothing that I could do about it, most physicians and most medical ethicists would say don’t test, because you don’t know what to do with it.
But if a drug comes out which can delay the appearance of disease from age 55 to 65, I’d be the first one to be tested, because then I could modify the appearance. So the concept is not just the knowledge of mutations, but the knowledge of a modifiable risk is quite important in medicine.
Personalized medicine sometimes is best defined by thinking about one woman speaking to another and saying, “You know, we both have breast cancer, but we don’t have the same disease, and that’s why we’re not treated the same way.”
And when we start looking at what’s causing the tumor to grow quickly in this breast cancer versus another, we see it’s driven by different genes, different proteins. And the more we understand that, the more we try to specifically turn off that gene that’s specifically activating a patient’s tumor.
I was starting, in my last job, developing experimental diagnostics — experimental therapeutics — working more with industry in terms of clinical trials, in terms of moving some of our ideas and hypotheses toward drugs. But I wanted to go to a place which actually wanted to really incorporate the new knowledge.
The knowledge of genetics, the knowledge of immunology … and bring it to drive drug development, and I felt that AbbVie had that intention, had that motivation, and the company was poised to actually do that transition from a more traditional pharmaceutical company to a science-driven biopharma company

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