# Precision lung cancer therapy design through multiplexed adapter measurement

> **NIH NIH U01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $434,529

## Abstract

Project Summary
Combination therapy holds considerable promise for overcoming intrinsic and acquired resistance to targeted
therapies but will rely on our ability to precisely identify the best drug combination for particular tumors. While
immense focus exists on using genomic information to direct therapeutic approach, many resistance
mechanisms do not rely on genetic changes and, in fact, can arise from entirely tumor-extrinsic factors within
the microenvironment. For example, though the receptor tyrosine kinase (RTK) AXL is widely implicated in
resistance to targeted therapies such as those directed against EGFR, its regulation by phosphatidylserine, as
opposed to mutation, amplification or autocrine ligand, make identifying the tumors that will respond to AXL-
targeted therapy especially challenging.
 We propose to study both downstream and receptor-proximal signaling during bypass resistance
mediated by AXL, and then across a wider panel of RTKs. Integrating these measurements with quantitative
modeling will identify the connectivity between receptors, interacting adapters, and downstream signaling
events, thereby defining the essential set of signaling network changes required for tumor cell survival in
response to targeted therapeutics. We will then apply this understanding by measuring RTK-adapter
interaction using proximity ligation to predict the RTKs driving bypass resistance and test these predictions in a
panel of patient-derived xenograft tumors.
 This work will considerably improve our ability to identify effective drug combinations by (a) developing
a mechanism-based assay for identifying which among many RTKs tumor cells are relying upon for survival,
(b) improving our basic understanding of exactly how network-level bypass resistance arises due to activation
of non-targeted RTKs both at the receptor-proximal and downstream signaling layer, and (c) expanding our
understanding of the RTK AXL with links to resistance, tumor spread, and immune avoidance.

## Key facts

- **NIH application ID:** 9998673
- **Project number:** 5U01CA215709-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** ERIC B. HAURA
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $434,529
- **Award type:** 5
- **Project period:** 2017-09-25 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9998673

## Citation

> US National Institutes of Health, RePORTER application 9998673, Precision lung cancer therapy design through multiplexed adapter measurement (5U01CA215709-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9998673. Licensed CC0.

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