# Preclinical studies of KRAS and EGFR mutations in lung cancer PDXs

> **NIH NIH U54** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2022 · $200,000

## Abstract

PROJECT SUMMARY/ABSTRACT
This application is being submitted in response to the Notice of Special Interest (NOSI) identified as NOT-CA-
22-039. Lung cancer is the leading cause of cancer incidence and mortality in all Americans but
disproportionally high in communities of color. Compared to Whites, for example, African Americans and
Latinos are 18% and 16% less likely to have an early lung cancer diagnosis, respectively. The 5-year survival
of African Americans and Latinos is also 21% and 16% lower than White patients. However, the incidence and
mortality rates in US minority populations are closely linked to their smoking rates. In African American and
some Asian/Pacific Islander groups such as Hawaiian and Samoan, lung cancer is the top cause of cancer
mortality. Lung cancer disproportionally affects African American men, who have incidence and mortality rates
of 15% and 18% higher than White men. Even in Latinos, the ethnic group with the lowest smoking rates in the
nation, lung cancer remains the first cause of cancer mortality in men. EGFR and KRAS are the most common
mutations in lung tumors and are strongly associated with race, smoking, and genetic ancestry. KRAS is
commonly diagnosed in Whites and African Americans, in men and smokers/former smokers. Asians and
Latinos, on the other hand, have a significantly lower frequency of KRAS mutations but are enriched with
mutations in EGFR. EGFR mutations in Asian and Latino patients are prevalent in never smoker women. Until
recently, most of the targeted therapies for lung cancer were developed for EGFR mutant tumors, while KRAS
was considered “undruggable.” This, however, changed in the last 12 months with the FDA approval of
sotorasib, a molecule that increases overall response rate and progression-free survival in tumors carrying the
KRAS G12C mutation. Despite these important advances, a significant fraction of patients either lack
response or develop resistance to EGFR and KRAS targeted therapies. In this supplement, we are leveraging
the resources of our minority PDX (MPDX) center to investigate mechanisms associated with response to
inhibitors for KRAS and EGFR in models from White and minority patients. Our Specific Aims are as follows:
Aim 1. To determine the activity of direct KRAS G12C inhibition of sotorasib in the presence or absence of dual
inhibition of glycolysis and glutaminolysis with sapanisertib and telaglenastat (CB839) in KRAS G12C mutant
PDXs with clinically relevant co-alterations (p53/Keap1). Aim 2. To carry out a feasibility study for identifying
biomarkers associated with EGFR inhibitor resistance in lung PDXs from Asian and White patients. This
project will increase our understanding of responses to targeted therapies for lunch cancer and serve as a
springboard for future clinical trials on precision medicine in white and minority patients.

## Key facts

- **NIH application ID:** 10582478
- **Project number:** 3U54CA233306-01S4
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Luis Guillermo Carvajal Carmona
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $200,000
- **Award type:** 3
- **Project period:** 2022-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10582478

## Citation

> US National Institutes of Health, RePORTER application 10582478, Preclinical studies of KRAS and EGFR mutations in lung cancer PDXs (3U54CA233306-01S4). Retrieved via AI Analytics 2026-06-15 from https://api.ai-analytics.org/grant/nih/10582478. Licensed CC0.

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