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UNC Lineberger’s Matthew Milowsky, MD, and Chelsea Osterman, MD, co-wrote an editorial in the journal Cancer on efforts to optimize a new precision medicine approach for treating the most common type of bladder cancer, urothelial carcinoma, once it’s spread in the body.

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UNC Lineberger’s Matthew Milowsky, MD.

“For the great majority of metastatic urothelial carcinoma, there is not a cure. There are now a number of new treatments available to patients with this disease that are allowing more patients to live longer than before. However, we still need to better understand which treatment is best for each patient, and we need to continue to develop new options for patients that do not respond to the currently available therapies,” said Osterman, who is a clinical fellow in the UNC School of Medicine Division of Hematology/Oncology. She co-wrote the editorial with Milowsky, who is the George Gabriel and Frances Gable Villere Distinguished Professor of Bladder and Genitourinary Cancer Research, the section chief of genitourinary oncology and co-director of the Urologic Oncology Program.

The editorial detailed advances and challenges for use of therapies designed to target FGFR, or Fibroblast Growth Factor Receptors, in metastatic urothelial cancer. The U.S. Food and Drug Administration has approved an oral therapy targeting FGFR in metastatic urothelial cancer, and researchers reported other inhibitors are under study.

Researchers reported that patient genetic alterations, screening methods for alterations in FGFR genes, the location of the patient’s cancer, and other factors could be important to optimizing response to the treatments.

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Chelsea Osterman, MD.

“The treatment of urothelial cancer has changed dramatically in the past few years and is continuing to evolve at a rapid pace,” Osterman said. “The success of FGFR inhibitors and other targeted therapies depends on improving our understanding of the ideal combination of genetic alteration, screening test, cancer type, and drug. We are starting to understand some of the pieces of this puzzle, but we still have a lot to learn in order to treat patients as effectively as possible.”

In regard to screening, they reported there are multiple ways to detect mutations in a FGFR gene, and the right method is needed to detect the type of alteration a patient has. Osterman also said that while most urothelial cancers start in the bladder, some start in part of the kidneys or ureters, and this could also impact drug responses.

“While we typically treat urothelial cancer the same way regardless of where it came from, there might be certain treatments that work better depending on where the cancer started,” she said.

“Advances in our understanding of the genes involved in urothelial cancer has led to the development of new medications that can specifically target these genes,” she also said. “This is an exciting new treatment strategy, but more research is needed to understand all of the factors that impact whether a patient responds to these treatments.”

Authors and Disclosures

The research was partially supported by a National Service Research Award Post-doctoral Traineeship from the Agency for Healthcare Research and Quality, sponsored by the Cecil G. Sheps Center for Health Services Research at UNC-Chapel Hill.

Conflict of interest: Milowsky has received grants from Merck, Acerta Pharma, Roche/Genentech, Bristol-Myers Squibb, Seattle Genetics, Incyte, Astellas Pharma, Clovis Oncology, Inovio Pharmaceuticals, AstraZeneca, X4 Pharmaceuticals, Mirati Therapeutics, Boehringer Ingelheim, Constellation Pharmaceuticals, Jounce Therapeutics, Syndax, Innocrin Pharma, MedImmune, Cerulean Pharma, and consulting fees from Asieris.