# Targets for Therapy for Carcinomas of the Lung

> **NIH NIH P01** · SLOAN-KETTERING INST CAN RESEARCH · 2020 · $1,705,771

## Abstract

Project Summary/Abstract
Since biologic events underlie clinical outcomes, we hypothesize that unraveling mechanisms of
intracellular signaling and metastasis in lung cancers will lead to the identification of new targets
for therapy for these illnesses and for individual patients. Our experience developing EGFR and
ALK kinase inhibitors, and the discoveries that mutations in EGFR and KRAS and ALK-
rearrangements underlie sensitivity and resistance to targeted therapies, have shown the
practicality and potential of this approach. Our 4 research projects and 3 cores propose to
continue a decade long iterative research process uniting clinical and laboratory observations.
These efforts have linked genetic aberrations in tumors to outcomes in patients and identified
agents targeting these same aberrations that benefit persons with lung cancers. This grant
embraces investigators, technologies, and pathways, each focused by specific clinical
questions, proposing to identify targets for therapies in lung cancers. Project 1 (Massagué)
identifies mediators of metastasis and immune evasion that can serve as targets for
intervention. Project 2 (Rosen) probes signaling in BRAF- and KRAS-driven lung cancers.
Project 3 (Lovely) investigates mechanisms and modulators of sensitivity and resistance to
EGFR and ALK kinase inhibitors. Project 4 (Lowe) uses mouse models and RNA interference to
interrogate KRAS- driven lung cancers focusing on combinatorial strategies including the allele
specific inhibitors studied in Project 2 and probing the impact of therapy-induced senescence on
immune surveillance. Our Molecular Profiling and Pathology Core crystallizes more than a
decade of experience in precise pathologic characterization, and use of the next-generation
technologies for comprehensive molecular profiling of lung cancers. The Biostatistics and
Bioinformatics Core ensures consistency in biostatistical analyses and provides projects and the
Pathology Core with analytic capabilities for genomic data. The Administrative Core has created
an organizational structure that assures integration and interaction by facilitating communication
and dissemination of findings and providing a forum for the principal investigators, leaders, and
the Executive and Scientific Advisory Committees to conduct scientific review and integration of
new opportunities to accelerate progress.

## Key facts

- **NIH application ID:** 9999409
- **Project number:** 5P01CA129243-13
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** MARK G. KRIS
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,705,771
- **Award type:** 5
- **Project period:** 2007-07-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9999409

## Citation

> US National Institutes of Health, RePORTER application 9999409, Targets for Therapy for Carcinomas of the Lung (5P01CA129243-13). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9999409. Licensed CC0.

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