# Kinase Inhibition in Kidney Cancer

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $432,423

## Abstract

ABSTRACT
The incidence of renal cell carcinoma (RCC) is on the rise. 65,000 new cases occur annually in the United
States. Vascular endothelial growth factor receptor (VEGFR) and mammalian target of rapamycin (mTOR)
inhibitors are FDA approved and commonly used treatments for advanced RCC but result in increases in
overall survival by only months. At this time, the most druggable portion of the genome remains the kinome.
Through unbiased, high-throughput screening we have identified and validated the therapeutic value of a novel
kinase in RCC, tyrosine kinase 2 (TYK2: a member of the Janus Kinase family) and demonstrate that it plays a
role in mTOR inhibitor resistance. We have characterized a signaling network in which TYK2 positively
regulates the SRC family kinases (SFKs) and demonstrate that dual inhibition of mTOR and SRC with
everolimus and dasatinib induces tumor regression in vivo. Based on these results we hypothesize that
inhibition of the TYK2/SRC axis is a tractable therapeutic strategy in a subset of RCC, that we can define
predictive markers of TYK2/SRC inhibitor response, and that defining the kinomic landscape of RCC and its
response to mTOR inhibition will lead to further combinatorial targets.

## Key facts

- **NIH application ID:** 9988187
- **Project number:** 5R01CA202053-05
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** WILLIAM Y. KIM
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $432,423
- **Award type:** 5
- **Project period:** 2016-09-02 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9988187

## Citation

> US National Institutes of Health, RePORTER application 9988187, Kinase Inhibition in Kidney Cancer (5R01CA202053-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9988187. Licensed CC0.

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