Combination therapies for Diffuse Midline Glioma (DMG) treatment

Unmet Need: Effective therapies addressing tumor heterogeneity for Diffuse Midline Glioma (DMG)

Diffuse Midline Glioma (DMG) is an incurable and universally lethal tumor type that emerges in the central nervous system and predominantly affects young children. DMG is characterized by significant tumor heterogeneity, which confers rapid resistance to therapeutic attempts with single drugs. These challenges hinder the development of targeted therapies, as most strategies fail to address the molecular complexity and cell-state diversity of the tumor. Currently, the only available treatment for DMG is palliative radiation therapy, which is non-specific and provides only short-term efficacy.

The Technology: Targeted combination therapies for Diffuse Midline Glioma based on identification of Master Regulator proteins

The technology describes a combination of anti-cancer therapeutics for targeting Diffuse Midline Glioma (DMG) that addresses tumor heterogeneity based on inverting the activity of DMG Master Regulator (MR) proteins, key proteins that determine cell state in individual tumor cells. This technology harnesses a precision medicine platform for discovering MRs in DMG, which represent pharmacologically accessible targets across DMG cell states. Thus, this approach enables the identification and screening of combinations of actionable drugs across heterogeneous DMG tumors, as well as accurate prediction of the efficacy of drugs capable of inverting MR activity in DMG patients.

This technology has been validated with cultured tumor cells derived from patients and patient cell line-derived DMG mouse models, demonstrating a reduction in tumor volume and significant survival benefit.

Applications:

Treatment for Diffuse Midline Glioma (DMG)
Targeted drug development for DMG
Diagnostic tools to predict drug efficacy
Personalized treatment for DMG based on tumor state heterogeneity
Stratification of patients in clinical trials based on tumor state
Research tool for Master Regulator proteins in DMG biology
Reconstruction of regulatory networks for cancers

Advantages:

Precision targeting of tumor heterogeneity
Synergistic combination treatment
Addresses underlying mechanisms of DMG pathogenesis
Precision medicine platform enables accurate prediction of drug efficacy in patients

Lead Inventor:

Andrea Califano, Ph.D.

Patent Information:

Patent Pending

Related Publications:

Fernández EC, Tomassoni L, Zhang X, Wang J, Obradovic A, Laise P, Griffin AT, Vlahos L, Minns HE, Morales DV, Simmons C, Gallitto M, Wei HJ, Martins TJ, Becker PS, Crawford JR, Tzaridis T, Wechsler-Reya RJ, Garvin J, Gartrell RD, Szalontay L, Zacharoulis S, Wu CC, Zhang Z, Califano A, Pavisic J. “Elucidation and Pharmacologic Targeting of Master Regulator Dependencies in Coexisting Diffuse Midline Glioma Subpopulations.” bioRxiv [Preprint]. 2024 Mar 17

Tech Ventures Reference:

IR CU24228
Licensing Contact: Joan Martinez