# Bay Area Team Against Resistance

> **NIH NIH U54** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $1,149,528

## Abstract

PROJECT ABSTRACT
The proposed Bay Area Team Against Resistance U54 Project (BATAR-UP) is an interdisciplinary effort of
investigators to apply their knowledge and expertise to dissect the molecular and cellular basis of incomplete
response and resistance to current treatments and to identify new treatment strategies to better neutralize or
eliminate residual disease and prevent resistance. This translational approach will be part of the NCI's Drug
Resistance and Sensitivity Centers Network to develop innovative strategies to understand and combat
mechanisms of tumor resistance and exploit tumor sensitivity to anti-cancer therapies.
 To accomplish this, BATAR-UP will support two projects and one core driven by a multidisciplinary
team of investigators at UCSF and Stanford University. Project 1 will define and interrogate the molecular and
cellular basis of residual disease in lung cancers treated with targeted inhibitors in clinical use. We will prioritize
for initial study both EGFR-mutant and ALK gene rearrangement positive lung cancers, given their importance
as key molecular disease subtypes and our prior published work and expertise. We will harness genetic and
transcriptomic analysis of clinical samples (liquid and tumor biopsies) to provide a molecular view of the
evolution of response, residual disease, and acquired resistance. We will generate organoid and PDX models
and apply cutting-edge functional screens (genetic, pharmacologic, and targeted proteomic assays) to identify
key vulnerabilities that could be therapeutically exploited, including with CTEP agents. This systematic
approach will allow us to reveal the basis of the incomplete response and residual disease that drives EGFR
and ALK inhibitor resistance and pinpoint therapeutic strategies to intercept the evolution of residual disease
and eventual acquired resistance. Project 2 will define and interrogate the molecular and cellular basis of
resistance and residual disease in lung cancers treated with current immunotherapies, including PD-1 and PD-
L1 antibodies. Leveraging shared platforms in synergy with Project 1, we will perform systematic analyses of
liquid and tumor biopsy specimens (and ex vivo models) obtained from patients longitudinally before and
during treatment and upon acquired resistance. We will focus our studies on EGFR and ALK wild type patients,
including squamous cell lung cancer and adenocarcinoma patients where immunotherapy has shown efficacy
but is typically non-curative. We will leverage (1) a novel lung cancer organoid model wherein tumor biopsies
are cultured as both tumor epithelium and their endogenous tumor infiltrating lymphocytes (TILs) en bloc as a
cohesive unit, and (2) deep droplet-based single-cell RNA-seq analysis. Our systematic approach will help
define the basis of the incomplete response and residual disease that contributes to immunotherapy resistance
and identify potential new therapeutic strategies to help convert these incomplete respon...

## Key facts

- **NIH application ID:** 10241307
- **Project number:** 5U54CA224081-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Trever G Bivona
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,149,528
- **Award type:** 5
- **Project period:** 2017-09-30 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10241307

## Citation

> US National Institutes of Health, RePORTER application 10241307, Bay Area Team Against Resistance (5U54CA224081-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10241307. Licensed CC0.

---

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