# A Rational Systematic Approach to Find Combinations of Pharmacologic and Immune Therapies that Target Identifiable Oncogenic States

> **NIH NIH U01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2021 · $942,132

## Abstract

A Rational Systematic Approach to Identify Combinations of Pharmacologic and Immune
Therapies that Target Identifiable Oncogenic States.
 
Abstract
Efforts to sequence large number of human cancers have provided a rich catalog of the most
common genetic alterations that driven cancer formation and maintenance. This increasingly
accurate mutational landscape has led to the identification of novel targets for therapeutic
interventions. However, there is widespread biological and clinical heterogeneity in tumors, even
when they share the same driver oncogene mutation. In addition, a high degree of dynamic
plasticity and adaptability makes cancers display complex patterns of acquired resistance that
manifest clinically. In a similar way, the wide variability of clinical responses to immunotherapy
and the onset of immune escape, are becoming a formidable obstacle to fully realize the
potential of many new and potentially effective immunotherapies. In this project we will
evaluate a rational systematic approach to characterize oncogenic states and their most salient
genomic and immune hallmarks in order to infer optimal combinations of pharmacologic and
immunological perturbagens that disrupt cancer cell and tumor microenvironment interaction
and viability. Our approach is based on our preliminary data, which suggests that in each
identifiable oncogenic state there is a close interplay between activation of oncogenic elements,
cellular pathways and the immune microenvironment. The project will test this approach with
three Specific Aims: Aim 1. Characterize 5-10 pan-cancer oncogenic states with well-defined
genomic and immune hallmarks including their specific molecular targets and sensitivity to
perturbagens. Aim 2. Computationally infer optimal combinations of pharmacological and
immunological perturbagens. Aim 3. Experimentally validate single and combinations of
perturbagens identified in Aim 2. This innovative approach will provide a rich source of CTD2
datasets and resources including a catalog of oncogenic states, their most salient genomic and
immune hallmarks, associated targets and validated combinations of pharmacologic and
immune therapies that are effective at targeting tumors. These results will lead directly to the
development of clinical trials, novel treatment strategies and provide the foundation for a new
generation of more comprehensive, functional-based, precision medicine approaches.

## Key facts

- **NIH application ID:** 10226232
- **Project number:** 5U01CA217885-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Ezra Cohen
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $942,132
- **Award type:** 5
- **Project period:** 2017-09-12 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10226232

## Citation

> US National Institutes of Health, RePORTER application 10226232, A Rational Systematic Approach to Find Combinations of Pharmacologic and Immune Therapies that Target Identifiable Oncogenic States (5U01CA217885-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10226232. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*