Tumor Tissue Analysis Provides Insight Into Tumor Heterogeneity

Bishoy M. Faltas, MD, assistant professor of medicine and director of bladder cancer research at the Caryl and Israel Englander Institute for Precision Medicine at Weill Cornell Medicine, discusses the significance of studying the response of tumor tissue to mutation-targeted agents in urothelial cancer.

In a study from Weill Cornell Medicine, investigators used a patient-derived organoid (PDO) based on cancerous urothelial tissue to test its response to the targeted therapies erdafitinib (Balversa), alpelisib (Piqray), and abemaciclib (Verzenio) for FGFR3, PIK3CA, and CDKN2A mutations, respectively.

According to Faltas, the investigators were able to analyze which cells responded to each biomarker-targeted inhibitor in order to gain a better understanding of why tumors show resistance to targeted therapies even when the right biomarker is present.

This study highlights the role of tumor heterogeneity on the efficacy of targeted therapies, Faltas says. Outcomes for patients can be improved by predicting the level of response based on tumor DNA. This can provide physicians a better understanding of drug sensitivity and resistance and lead to more effective approaches using combination therapies.

TRANSCRIPTION:

0:08 | In one instance, we took a PDO from a urothelial cancer or bladder cancer. We then performed whole-exome sequencing and identified a PIK3CA mutation, an FGFR3 mutation, and a CDKN2A deletion in that particular organoid. We were able to test different targeted agents against each of these genomic alterations. We found that we could actually track the evolution of the cancer cells, which cancer cells are going to be killed by the cancer drug—for example, the FGFR3 inhibitor—and which cancer cells are not going to be killed by the drug that are within the same organoid.

0:54 | So there is a concept called tumor heterogeneity, meaning that there are different cancer cells with different genetic makeups within the same tumor. We're finding that some of these cells may respond to a different drug, whereas some of the other cancer cells within the same tumors would not respond to the same drug. And in this study, we were able to actually show that, using single-cell DNA sequencing.