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Can Genetic Signatures Predict Tumor Response to Immunotherapy in Bladder Cancer?

By: Kayci Reyer
Posted: Wednesday, August 31, 2022

Research presented in the Journal of the National Cancer Institute suggests that the presence of certain genetic signatures associated with collagen receptors may predict a tumor’s response to immunotherapy in bladder and other cancers. Dan Theodorescu, MD, PhD, Director of the Cedars-Sinai Cancer Center in Los Angeles, and colleagues noted that these biomarkers may help to identify tumors that are more or less likely to respond to anti-PD-1/PD-L1 immune checkpoint therapies, thereby steering decision-making about appropriate treatments.

The study focused on discoidin domain receptor tyrosine kinase 2 (DDR2), which was recently implicated as a factor in anti–PD-1 resistance in animal models, and DDR1, which is in the same family. DDR1 and DDR2 gene signatures were derived using transcriptome analysis of tumors grown in mice. In human tumors, DDR1 and DDR2 had inverse gene-expression patterns—tumors with high DDR1 expression had low DDR2 expression, and vice versa. Although tumors with high expression of DDR2 demonstrated active immune pathways and characteristics associated with a T-cell–inflamed phenotype, tumors with high expression of DDR1 had traits consistent with a non–T-cell–inflamed phenotype, resembling those of immune “excluded” tumors. Though tumors with high expression of both DDR1 and DDR2 signatures were associated with poor overall survival, those with only high expression of DDR2 were associated with worse overall and progression-free survival.

“The next step is to further evaluate these signatures in larger data sets obtained from completed or ongoing prospective clinical trial,” said Dr. Theodorescu in a Cedars-Sinai press release. “This could yield new tools that allow clinicians to determine pretreatment whether given patients will likely respond to anti–PD-1/PD-L1 therapy. They can then proceed with anti–PD-1/PD-L1 therapy for those patients who will derive the most benefit and offer alternative therapies for patients not likely to respond, improving outcomes for all.”

Disclosure: For full disclosures of the study authors, visit academic.oup.com.


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