# Characterizing treatment responses for common lung cancer (LC) subtypes in Latinos and Asians

> **NIH NIH U54** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2023 · $288,306

## Abstract

SPECIFIC AIMS
The purpose of UCaTS Project 2 is to target clinically important genomic markers of early resistance to EGFR
tyrosine kinase inhibitors (EGFR-TKIs) in EGFR-mutant non-small cell lung cancer (NSCLC), to develop
quantitative models of Receptor Tyrosine Kinase (RTK)-driven signaling pathways under inhibition, and to
explore the role race, ethnicity and genetic ancestry has in predicting baseline EGFR signaling and EGFR-TKI
treatment response. EGFR-mutant NSCLC comprises a substantial subset of lung adenocarcinoma (15% in
Western/White populations) and occurs with a higher frequency in Asian Americans, Native Hawaiians, Pacific
Islanders (AANHPI ~50%), and Latinos (~38%). EGFR mutations show strong associations with smoking status,
gender, race/ethnicity, and genetic ancestry. Women of AANHPI and Latino race/ethnicity have, compared to
non-Latino Whites (NLW), lower smoking rates and higher frequency of EGFR mutant tumors. Interestingly, a
recent study showed that high Indigenous American Ancestry (which is closely associated with Asian ancestry)
confers a higher risk of developing EGFR-mutant lung cancer in Latinos. This suggests that somatic EGFR
mutations have close associations of biological and non-biological aspects associated with race/ethnicity or
ancestry. Through this research, we will develop novel therapeutic strategies with combinations of FDA approved
and NCI-CTEP drugs to translate into NCI-sponsored clinical trials overcoming EGFR-TKI resistance
mechanisms associated in EGFR-mutant NSCLC. We will also assess whether race/ethnicity and genetic
ancestry impacts EGFR signaling and influences responses to EGFR inhibition.
 Patient-derived xenografts (PDXs) have been broadly used in lung cancer research and drug development.
We have extensive experience in establishing PDXs and conducting PDX-based research. Through the Jackson
Laboratory (JAX), UCSF and UT Southwestern collaborations, we established and characterized over 200 lung
cancer PDXs in which 25 have EGFR-activating mutations and we have identified an additional 10 EGFR-mutant
lung cancer models in PDXnet. We anticipate that UCaTS will generate at least 25 additional EGFR-mutant
PDXs. We have performed detailed histopathological and genomic characterization on many of these PDXs
focused on oncogene driven NSCLC where we identified multiple putative resistance mechanisms that mediate
early resistance to current EGFR-targeted therapeutic approaches in these models. We have also shown that
EGFR-mutant PDXs can potentially be used to optimize treatment combinations to overcome EGFR-TKI
resistance and to identify the most efficacious drugs or drug combinations including FDA approved and NCI-
CTEP agents. We will use a high-content live-cell imaging platform to analyze intracellular EGFR signaling, which
provides a high-resolution assessment of cellular adaptation to inhibition. The work for this project arises out of
our current research, which will be used to address th...

## Key facts

- **NIH application ID:** 10733396
- **Project number:** 1U54CA283766-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Jonathan W Riess
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $288,306
- **Award type:** 1
- **Project period:** 2023-08-01 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10733396

## Citation

> US National Institutes of Health, RePORTER application 10733396, Characterizing treatment responses for common lung cancer (LC) subtypes in Latinos and Asians (1U54CA283766-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10733396. Licensed CC0.

---

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