# Oncogenic mechanisms, molecular stratification and therapeutic targets of brain tumors

> **NIH NIH R35** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2024 · $874,950

## Abstract

Abstract
The work to be pursued in this application will continue and expand the program pioneered by Dr. Iavarone to
combine innovative computational tools and state-of-the-art experimental cancer models in vitro and in vivo to
identify homogeneous subgroups of cancer patients in order to dissect the pathogenesis of cancer and design
tailored and fully validated personalized therapeutic approaches. The application is focused on glioblastoma
multiforme, one of the most lethal forms of human cancer. The investigation of glioblastoma has represented a
long-standing effort of Dr. Iavarone’s laboratory, which in recent work has produced novel targeted therapeutic
opportunities currently being tested in clinical studies. The proposal will also benefit from the organizational
contexts recently set in motion by the large network operations coordinated by the PI. The research plan is
articulated around the development of a novel and integrated computational-experimental framework for: i) the
identification of homogeneous groups of tumors sharing activation of the same biological pathways; ii) the study
of cancer heterogeneity at the single cell level to accurately inform tumor classifications; iii) the therapeutic
prediction emerging from the identification of driver modules and synthetic lethal relationships of malignant
glioma. We will develop and apply novel technologies for high-throughput transcriptomic and proteomic analysis
of individual cells within malignant glioma tissues. These approaches, which we have pioneered in our laboratory
at Columbia University during the last few years, will serve as the basis for the multifaceted computational
analysis that will extract genes and proteins responsible for the phenotypic state of individual cells. Experimental
validations will be selectively applied to the novel and most exciting molecular pathways and will be performed
by our laboratory that has an array of experimental tools and sequence-annotated patient-derived models to
pursue each individual question. As for the selection of oncogene-dependent and independent vulnerabilities
identified by our previous work, the ability of our studies to identify novel driver phenotypes and master regulators
of individual tumor cells will be geared towards routing the new mechanisms into pathway-based synthetic
lethality that will inform specific drug sensitivities. The successful outcome of this proposal is an integrated
computational-experimental pipeline that will be able to mechanistically identify the determinants of tumor
genomes and phenotypes of solid tumors. This information will be of invaluable significance to decipher evolving
tumor dependencies and provide the most accurate therapeutic predictions.

## Key facts

- **NIH application ID:** 10922735
- **Project number:** 5R35CA253183-05
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** Antonio Iavarone
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $874,950
- **Award type:** 5
- **Project period:** 2021-09-24 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10922735

## Citation

> US National Institutes of Health, RePORTER application 10922735, Oncogenic mechanisms, molecular stratification and therapeutic targets of brain tumors (5R35CA253183-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10922735. Licensed CC0.

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