# Project 2: Delta Stromal Ecology of NSCLC

> **NIH NIH U54** · H. LEE MOFFITT CANCER CTR & RES INST · 2023 · $481,470

## Abstract

Project 2 abstract
Project 2 will investigate the changes in neoplastic and stromal compartments during the acquisition of
resistance to ALK and KRAS targeting therapies, with specific emphasis on the therapy-sheltering impact of
the stromal niche, observed in multiple experimental models. Despite the growing appreciation of the potential
contribution of stromal on the sensitivity of tumor cells to targeted therapies, there are no established
conceptual frameworks and experimental pipelines to account for this effect on evolving resistance.
Confounding the challenge, acquired resistance cannot be understood just with before-after snapshot
analyses, as the sensitivity of tumor cells to therapies, stroma-tumor ratio, and stromal composition and effect
are dynamically changing over the course of treatment. To understand the Decology of acquired resistance we
will perform system-level characterization of temporal and spatial phenotypic changes within the tumor and
stromal compartments, including changes in proliferation/death and clonal dynamics. These changes will be
captured in the formalism of in silico models through careful integration of experimental and modeling tools.
The quality and utility of the models will be assessed by making experimentally testable predictions. Following
calibration, the models will be used to find novel strategies for combination therapies that optimize long-term
remission. Initial model development and calibration will be performed in a xenograft model of ALK+ NSCLC
that has been the focus of our recent interdisciplinary studies. Subsequently, we will use the pipelines to gain
an understanding of the eco-evolutionary dynamics of other xenograft and syngeneic models of ALK+ and
KRASG12C NSCLC. These studies will help develop the robust knowledge base required for the development
of novel and impactful translational strategies.

## Key facts

- **NIH application ID:** 10730406
- **Project number:** 1U54CA274507-01A1
- **Recipient organization:** H. LEE MOFFITT CANCER CTR & RES INST
- **Principal Investigator:** Andriy Marusyk
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $481,470
- **Award type:** 1
- **Project period:** 2023-09-15 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10730406

## Citation

> US National Institutes of Health, RePORTER application 10730406, Project 2: Delta Stromal Ecology of NSCLC (1U54CA274507-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10730406. Licensed CC0.

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