This blog post was written by intern Amanda Garrison, a student at Florida State University. In this series, we aim to help readers understand certain scientific concepts about cancer. The concepts are topics from the Johns Hopkins Kimmel Cancer Center’s annual lecture series Fundamentals of Cancer, Cause to Cure which is directed by oncologist Leisha Emens, M.D., Ph.D. and available to researchers and staff working in the cancer center.
Most people have heard of and have a basic understanding of genetics, but have you ever heard of epigenetics? If not, then you’re in the same spot I was a few days ago.
By definition, the term epigenetics refers to heritable changes in gene expression that do not involve changes to the underlying DNA sequence; a change in phenotype without a change in genotype. It’s a regular and natural occurrence but can be influenced by several factors, such as age, lifestyle, and disease state. Epigenetic modifications can display as commonly as the manner in which cells differentiate to end up as skin cells, liver cells, brain cells, etc. Or, epigenetic change can have more damaging edicts that can result in diseases, such as cancer.
So, how does this scientific process apply to cancer treatments, and what are scientists finding out about it? Here’s some of the latest research underway at the Johns Hopkins Kimmel Cancer Center.
Drs. Stephen Baylin, Cynthia Zahnow, and Drew Pardoll studied patients with advanced lung, breast, and colon cancers in which an immune system-related gene called PDL1 was activated. Laboratory studies indicated that its expression in lung cancer cells may be enhanced by therapies that target epigenetic processes. Dr. Pardoll believes that using a drug to block PD-L1 or a similar gene called PD-1 in unison with epigenetic therapy could change the balance of immune effects of the treatment.
Scientists have also found that cancer cells play a bit of hide-and-seek with the immune system. But new research is revealing how to find cancer’s hiding spots.
Cancer has an immune evasion signal and, in order to survive, cancer cells need to partially adapt to their environment. When treated with epigenetic drugs, the ability to evade the immune system is broken and cancer cells are tricked into sending out signals for the immune cells to identify and destroy them. But they also express PD-L1 proteins to shield against immune attack. After going back to the lab with this knowledge, Drs. Baylin, Zahnow, Nita Abuja, and John Wrangle found that many genes get reactivated, but about 20 percent of them are related to immune regulation, which is a much bigger component than they thought, according to Dr. Ahuja.
They found a small subset of the genes they identified constitute a viral defense pathway that are epigenetically programmed to avoid detection by the immune system. By using a drug to reverse this programming, essentially performing a form of “viral mimicry,” scientists may be able to force the cancer cells out of hiding and make them more vulnerable to treatment, or better yet, allow the immune system to kill the cancer altogether.
Read more about epigenetics.