An “Epi” Sort of Genetics: What is Epigenetics and How Does It Impact Cancer?

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.

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paul November 24, 2015 at 11:40 pm

Great insight, Cancer" isn't a disease it's a term used to describe about 200 different types of diseases. All cancers have a few things in common, however. They're caused by mutations in our genetic material that make cells behave abnormally. They grow out of control and may destroy the cells around them or spread to other tissues. These mutations also keep the cells from dying according to their normal life cycle, which is part of why cancer cells can be so difficult to destroy.
Epigenetic therapy may be able to treat some types of cancers, and it may also be able to prevent them from developing in the first place.

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Gene DeBerardinis November 20, 2015 at 1:55 pm

My brother has stage 4 prostate cancer. He has completed taking the oral medications because they no longer worked. He has just started chemotherapy. When it no longer works his doctor
says experimental drugs/therapies are his only option. Who can we contact at John Hopkins
to find out what experimental therapies are available?
What other hospitals, labs should we explore?

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Vanessa Wasta December 7, 2015 at 3:42 pm

Our experts are available for consultations to discuss experimental and standard therapies tailored to each patient. Contact the New Patient and Referral Office by calling 410-955-8964 to schedule an appointment for a consultation. In addition, a database of open clinical trials at the Johns Hopkins Kimmel Cancer Center is available at: http://www.hopkinsmedicine.org/kimmel_cancer_center/research_clinical_trials/clinical_trials/.
As for other centers, you may want to seek other medical opinions from additional cancer centers designated by the National Cancer Institute. A list of NCI-designated centers, like the Johns Hopkins Kimmel Cancer Center, is available at: http://www.cancer.gov/research/nci-role/cancer-centers.

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