Fusion Gene Diagnostics and Targeted Treatments for Progressive Prostate and Other Cancers

This suite of patented technologies presents a groundbreaking approach to diagnosing, prognosticating, and treating aggressive prostate cancer and other malignancies by identifying and targeting specific oncogenic fusion genes through molecular detection and precision genome editing methodologies.

Description

This set of patented technologies from the University of Pittsburgh centers on discovering and utilizing fusion genes—such as TRMT11-GRIK2, SLC45A2-AMACR, MTOR-TP53BP1, and MAN2A1-FER—that are associated with the progression, recurrence, and metastasis of prostate and several other cancers. The inventions encompass advanced genome sequencing and transcriptome analysis methods to detect these fusion genes in patients. Further, therapeutic strategies including the application of genome editing tools like CRISPR/Cas9 and tyrosine kinase inhibitors are described, targeting fusion gene products to hinder cancer growth and improve patient survival. These technologies also propose diagnostic kits to aid in effective clinical decision-making by predicting disease outcomes and tailoring treatments accordingly.

Applications

- Clinical diagnostics for stratification of prostate cancer patients based on fusion gene profiling to identify those at elevated risk of recurrence, metastasis, and cancer-specific mortality.
- Guidance of personalized treatment decisions by utilizing fusion gene status as biomarkers predictive of aggressive disease and therapeutic responsiveness.
- Development of targeted therapeutics employing tyrosine kinase inhibitors to inhibit fusion gene-encoded aberrant kinase activity in cancers harboring MAN2A1-FER and related fusions.
- Implementation of genome editing techniques such as CRISPR/Cas9 to selectively inactivate pathogenic fusion genes in malignant cells, offering a novel intervention to halt cancer progression.
- Creation of prognostic kits and diagnostic panels for routine clinical use to detect fusion genes in biopsy or surgical specimens.
- Application across multiple cancer types including prostate cancer, liver cancer, glioblastoma, and potentially other malignancies characterized by similar fusion gene patterns.

Advantages

- Precision Medicine Enablement: By identifying specific fusion genes that drive aggressive cancer phenotypes, the technology allows for precision-targeted diagnostics and individualized treatment strategies.
- Prognostic Power: The strong correlation between fusion gene presence and adverse clinical outcomes enables early prediction of disease progression and recurrence, fostering proactive treatment management.
- Innovative Therapeutic Options: Integration of genome editing technologies offers a novel modality to directly disrupt oncogenic drivers at the genetic level, surpassing conventional chemotherapy efficacy and specificity.
- Broad Oncologic Utility: Identification of fusion genes across diverse tumor types extends the applicability beyond prostate cancer, enabling cross-disease therapeutic and diagnostic development.
- Comprehensive Validation: Supported by extensive experimental data including molecular assays, kinase activity profiles, animal model studies, and clinical correlations, underscoring robustness and reliability.
- Potential to Reduce Mortality and Morbidity: By improving detection accuracy and providing targeted treatment options, these technologies contribute to better patient outcomes with reduced side effects compared to nonspecific therapies.

Invention Readiness

In vivo data

IP Status

https://patents.google.com/patent/US20170240924A1; https://patents.google.com/patent/US9932641B2; https://patents.google.com/patent/US10167519B2;

Related Publication(s)

Chen, ZH., Yu, Y., Zuo, ZH. et al. Targeting genomic rearrangements in tumor cells through Cas9-mediated insertion of a suicide gene. Nat Biotechnol 35, 543–550 (2017). https://doi.org/10.1038/nbt.3843

Luo, J.-H., Liu, S., Zuo, Z.-H., Chen, R., Tseng, G. C., & Yu, Y. P. (2015). Discovery and Classification of Fusion Transcripts in Prostate Cancer and Normal Prostate Tissue. The American Journal of Pathology, 185(7), 1834–1845. https://doi.org/10.1016/j.ajpath.2015.03.008