Using cancer genetics to guide personalized treatment
Over 20 years ago, Steven Jones was a PhD student struggling to understand the genetic makeup of a tiny nematode worm called C. elegans. Scarcely a millimeter long, the worm soon made headlines as the world’s first fully sequenced animal genome.
As a key member of the sequencing team, Dr Jones was already looking ahead to the untapped potential of his field. “I believed that if there was one thing you could point genomics at it was cancer, being basically a disease that is genetically underpinned.”
Fast forward 2 decades and Dr Jones is now the associate director and head of bioinformatics at the Michael Smith Genome Sciences Centre of the BC Cancer Agency in Vancouver. With a staff of hundreds and millions of dollars in sequencing technology, he is tracking down the genetic changes that lead to cancer.
It’s complex detective work. One genetic change leads to another and then to many more before a tumour is formed. The changes are different in each type of cancer and sometimes even within a cancer type. Mapping all this is just the first step.
“The trick then is to understand what those changes might be doing. Why are they important in the formation of a tumour? Can we target that change? Are there tricks or tools or drugs that might act against it?” explains Dr Jones.
With funding from the Canadian Cancer Society, Dr Jones first asked these questions about breast cancer. He sequenced the DNA of different breast cancer cells and developed computational tools to look for any genetic mutations they share in common. Then he looked for drug compounds that might act on these mutations while leaving normal cells alone.
Building on this work, Dr Jones also sequenced the DNA of many thyroid cancers to understand how they differ at a molecular level from benign, or non-cancerous, thyroid growths.
Through these and other cancer DNA sequencing efforts, Dr Jones and his colleagues also discovered a new group of molecules called small non-coding RNAs that could discriminate between cancer and normal cells. These findings could lead to the development of new, cost-effective diagnostic tests.
Dr Jones foresees a day when doctors can genetically analyze tumour samples from every cancer patient. “This will give us a huge amount of information. We could tell from the mutations in that particular patient which treatment would be most effective. So it would herald the concept of what we call personalized medicine.”
For example, one of Dr Jones’ ongoing projects is to design a new treatment that can target a cancer-promoting mutation in the cyclin D1 gene that often occurs in lymphoma, a type of blood cancer. If the project is successful, this could lead to tailored therapy in lymphoma, which could increase survival.
Decades into his cancer genomics career, Dr Jones is still looking ahead. “I’m extremely excited about how this technology can be pointed at this disease. I really do feel that we will make fundamental insights into how we understand cancer and how we can personalize the treatment of it.”