NU 2020-155

INVENTORS
Joshua Meeks*
A Gordon Robertson
Clarice S. Groeneveld
Aurélien de Reyniès

SHORT DESCRIPTION
Using next-generation sequencing to classify patient subtypes of bladder cancer for targeted T1 tumor therapies

BACKGROUND
T1 bladder cancers have the highest progression and recurrence rates of all non-muscle-invasive bladder cancers. The standard treatment for T1 cancers is bacillus Calmette-Guérin (BCG). However, to date there are no biomarkers that could predict the response to BCG. Furthermore, there is minimal data regarding tumor-specific prognostic features. Current next-generation cancer diagnostics are limited due to a focus on monitoring progression into muscle or using PCR-based methods to classify survival populations.

ABSTRACT
This novel technique developed by NU scientists categorizes patients into bladder cancer subtypes based on tumor characterization, making it easier to prescribe patient-specific treatment options. This invention focuses on the early stage T1 bladder cancers by using RNA sequencing to classify patients into 5 populations based on tumor subtypes. These 5 clusters had distinct clinical outcomes and biological characteristics. Clusters were divided based on pathologic carcinoma (T1-LumGU), inflammation (T1-Inflam), MYC expression and tumor recurrence (T1-Myc and T1-Early), and luminal/urothelial differentiation (T1-TLum). Furthermore, clusters could be grouped into two categories based on regulons. An expression-based single-sample classifier has been developed by the inventors and validated across an additional cohort. Taken together, NU scientists demonstrate that T1 bladder cancers can be further categorized, potentially improving treatment outcomes by facilitating precision medicine based on subtypes. Differential expression quantified across clusters demonstrate the possibility of targeting specific genes based on the expression profiles of the patient subtypes.

APPLICATIONS  

• To risk-stratify patients with T1 bladder cancer
• To identify potential therapies for T1 bladder cancer

ADVANTAGES

• Categorizes specific bladder cancer subtype
• Enables physicians to provide more personalized and informed treatment options

PUBLICATION
Robertson AG, Groeneveld CS, Jordan B, Lin X, McLaughlin KA, Das A, Fall LA, Fantini D, Taxter TJ, Mogil LS, Lindskrog SV, Dyrskjøt L, McConkey DJ, Svatek RS, de Reyniès A, Castro MAA, Meeks JJ. (2020) Identification of Differential Tumor Subtypes of T1 Bladder Cancer. Eur Urol. 78(4):533-537. doi: 10.1016/j.eururo.2020.06.048. Epub 2020 Jul 17. Erratum in: Eur Urol. 2022 Feb;81(2):e53. PMID: 32684305.

IP STATUS
US patent and PCT applications have been filed.