This technology identifies epidermal growth factor receptor (EGFR) gene fusion events that are associated with various cancers, enabling diagnosis and targeted treatment.
Unmet Need: Targeted drug treatment of diverse cancers with reduced side effects
Current cancer treatments typically involve combinations of chemotherapy, surgery, and radiation. However, these therapies can have many side effects and are difficult to implement with aggressive cancers. Targeted drug therapies present a favorable alternative, since they are tailored to a specific form of cancer, increasing the likelihood for positive outcomes and reduced treatment associated side effects. While various oncogenes for targeted approaches have been discovered, there remains a need to understand downstream signaling targets and identify commonalities among diverse cancers, in order to facilitate personalized oncotherapy for all cancer patients.
The Technology: EGFR fusion proteins as diagnostic and therapeutic targets for personalized oncotherapy
This technology identifies specific EGFR fusion events and related downstream signaling targets associated with roughly 3-8% of cases across various cancers, including aggressive cancers with low survival rates. The technology implicates specific fusion events as integral to oncogenesis, and provides methods for decreasing expression of EGFR fusion proteins and administering targeted drug treatments. Additionally, this technology provides an innovative treatment strategy for aggressive cancers such as glioblastoma, which has a median survival rate of 12-15 months and few current treatment options. This technology has wide applicability for diagnosis and targeted treatment of diverse cancers, and may facilitate the development of more selective inhibitors against gene fusion associated cancers.
The causative effect of EGFR fusion events, as well as the therapeutic benefit of EGFR inhibitors, has been demonstrated in humanized mouse models of cancer.
Applications:
- Diagnostic for various cancers (i.e. glioblastoma, breast cancer, colorectal carcinoma, lung cancer, prostate cancer)
- Targeted treatment of various cancers (i.e. glioblastoma, breast cancer, colorectal carcinoma, lung cancer, prostate cancer)
- Identification of therapeutic cancer targets, especially EFGR pathway inhibitors
- Development of animal and cell culture-based models of cancers associated with EGFR fusion events
- Drug screening assays for EGFR fusion associated cancers
- Research tool to understand the relationship of EGFR-related pathway components to cancer and other diseases
Advantages:
- Fusion-specific inhibition allows for targeted drug treatments with possibly reduced side effects
- Complementary to other forms of chemotherapy and surgical interventions
- Potential personalized treatment strategies for patients identified with specific fusion events
Lead Inventor:
Antonio Iavarone, M.D.
Patent Information:
Patent Status
Related Publications:
Frattini V, Pagnotta SM, Tala, Fan JJ, Russo MV, Lee SB, Garofano L, Zhang J, Shi P, Lewis G, Sanson H, Frederick V, Castano AM, Cerulo L, Rolland DCM, Mall R, Mokhtari K, Elenitoba-Johnson KSJ, Sanson M, Huang X, Ceccarelli M, Lasorella A, Iavarone A. “A metabolic function of FGFR3-TACC3 gene fusions in cancer” Nature. 2018 Jan 11; 553(7687): 222-227.
Frattini V, Trifonov V, Chan JM, Castano A, Lia M, Abate F, Keir ST, Ji AX, Zoppoli P, Niola F, Danussi C, Dolgalev I, Porrati P, Pellegatta S, Heguy A, Gupta G, Pisapia DJ, Canoll P, Bruce JN, McLendon RE, Yan H, Aldape K, Finocchiaro G, Mikkelsen T, Privé GG, Bigner DD, Lasorella A, Rabadan R, Iavarone A. “The integrated landscape of driver genomic alterations in glioblastoma” Nat Genet. 2013 Oct; 45(10): 1141-1149.
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