Our bodies accumulate mutations in our DNA over our lifetime due to normal imperfections in the DNA replication process. While most mutations happen in places that do not have any important consequences, sometimes they happen in genes that make the cell better at growing and dividing, potentially leading to cancer.
Clonal evolution refers to the process by which tumors change over time and develop different properties such as resistance to treatments. Cancer cells tend to mutate more easily than normal cells, so they are constantly changing.
At the International Workshop on CLL (iwCLL) 2019, our own Dr. Brian Koffman interviewed Dr. Constantine Tam, a hematologist at the Peter McCallum Cancer Center in Melbourne, Australia. They discussed clonal evolution in CLL and how it can lead to resistance to certain treatments.
- When we treat CLL, it can change and mutate leading to the development of treatment resistance.
- It is important to understand why resistance develops and try to predict it so that we can hopefully prevent it in the future.
- Analyzing all the genes in a person’s body to try to predict treatment resistance is not useful because there is a lot of normal variation between individuals.
- CLL is very heterogenous, meaning that all CLL cells are not identical clones. There are lots of sub-clones that are a little bit different from each other.
- We now have the ability to look at the genetics of individual cancer cells. This allows scientists to try to determine what makes one cancer cell different from another cell and what changes might lead to treatment resistance.
- Targeted therapies are highly specific so that they only kill certain cells, but this also means that if there is a cancer cell with a resistance mutation it can evade treatment and multiply.
- The chances of a CLL cell being resistant to 2, 3, or 4 drugs at the same time is low, so by using combination therapies you should get a better response that lasts longer.
- The caveat is that even with our best combinations, we do not think they are curative (meaning, they can’t get rid of every last CLL cell), so patients are likely to have a small number of resistant cells that can cause relapse.
- A useful strategy may be to try to identify which cells are likely to mutate and cause resistance so that they can be targeted early on.
We have come a long way in our understanding of CLL and the technologies available to study it have advanced as well. Scientists are working to better understand the biological changes that lead to treatment resistance so that, hopefully, one day we will be able to predict which cells will develop resistance and stop them from turning into drug-resistant cells.
Please enjoy this interview with Dr. Tam from September 2019 at iwCLL in Edinburgh, Scotland.
Take care of yourself first.
Ann Liu, PhD