Researchers from Cedars-Sinai Cancer have discovered genetic fingerprints that can predict whether tumors in patients with bladder and other cancers would react to immunotherapy.
Their findings, which were published in the National Cancer Institute’s peer-reviewed journal, may one day help clinicians choose the best cancer treatments for their patients.
“Our work indicates that these genetic signatures may prove to be tremendously valuable in predicting immunotherapy response in patients with bladder cancer, but also other tumor types,” said Dan Theodorescu, MD, Ph.D., director of Cedars-Sinai Cancer, the PHASE ONE Foundation Distinguished Chair and senior author of the study. “We will continue investigating these biomarkers with the goal of bringing them into clinical use and improving patient outcomes.”
During the past five years, anti-PD-1/PD-L1 therapy–a type of cancer immunotherapy that paves the way for the body’s immune system to attack tumor cells–has proved effective against many cancer types, according to Keith Syson Chan, Ph.D., a translational scientist, professor of Pathology and co-author of the study.
“It has proven very effective against melanoma and revolutionized lung cancer treatment,” Chan said. “Bladder cancer is considered one of the more responsive tumor types, but still has just a 25% durable response rate, so improvement is still needed.”
When a tumor causes a host immune reaction, immune cells usually can infiltrate the core of the tumor, and scientists call it a “hot” tumor. Some tumors, on the other hand, block immune cells from infiltrating and are known as “cold” tumors.
A gene named discoidin domain receptor tyrosine kinase 2 (DDR2) was linked in previous work by Theodorescu to anti-PD-1 resistance in animal models of several tumor types. This new study used human cancer data sets in distinct tumor types in a partnership between cancer biologists and bioinformatics researchers to further analyze the DDR gene family.
Using bladder cancer as a model, Sungyong You, Ph.D., a computational biologist with experience in urologic oncology, examined data from The Cancer Genome Atlas program, a freely accessible database with details on hundreds of cancer samples. He examined how the expression of DDR2 and related gene DDR1 correlated with the host immune response to a tumor.
He also examined the correlation between the genes controlled by DDR2 and DDR1 (also known as gene signatures). Then, he examined patient data from IMvigor 210, a clinical trial that assessed the effectiveness of immunotherapy in treating bladder cancer, to determine whether these outcomes were correlated with the expression of DDR2 and DDR1 or their associated gene profiles.