# Investigation of the role of epithelial-mesenchymal plasticity in renal cell carcinoma

> **NIH NIH R01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2021 · $591,326

## Abstract

Sarcomatoid renal cell carcinoma (sRCC) represents an aggressive group of renal epithelial tumors
characterized by histopathological features of epithelial–mesenchymal plasticity (EMT) and prominent metastatic
behavior. These malignancies are extremely challenging in the clinic, as they fail to respond to the standard-of-
care therapeutic regimens for RCC. Furthermore, in spite of the remarkable advances in cancer genomics, there
are still no reliable tools or biomarkers to predict the clinical course of the disease, particularly in the context of
modern therapeutic interventions. Objectives. The long-term goal of this project is to identify the genomic and
molecular drivers of malignant progression in sRCC, focusing on the role of EMT in clonal evolution, in the
acquisition of metastatic potential and as a mechanism of adaptation to therapy. This will lead to the identification
of context-specific vulnerabilities dictated by the specific genomic and molecular landscapes that characterize
this aggressive subset of kidney cancer. Rationale and Hypothesis. Preliminary studies showing the
emergence of specific patterns of chromosomal alterations led us to the hypothesis that the acquisition of
chromosomal instability (CIN) during tumor evolution favors the selection of clones endowed with high cellular
plasticity and prominent metastatic potential. Specific Aims. In the first aim we will provide a detailed spatial
and temporal annotation of epithelial and mesenchymal population dynamics during malignant progression and
in response to pharmacological interventions. The second aim will define the genomic and transcriptomic
landscape of the malignant subpopulation and the interplay between these cellular compartments and the
components of the TME. In the third aim we will identify context-specific vulnerabilities, defining the genetic
dependencies of epithelial and mesenchymal cells. Significance. The approach will provide fundamental
information about clonal dynamics, tumor–host interactions at a single-cell resolution, and tumor evolution in
RCC, substantially improving our understanding of the genetic and molecular bases of the disease.
Translational relevance. A detailed understanding of the genetic and molecular events driving malignant cell
plasticity and the evolution to sRCC will provide the framework to predict the behavior of this heterogeneous
group of tumors. Furthermore, the functional genomic approach will uncover context-specific vulnerabilities and
provide novel drug targets in a disease class in urgent need of effective treatments. Innovation. The project is
innovative from a conceptual and technological standpoint. Targeting cancer-specific weaknesses emerging in
the context of cell plasticity, increased tumor heterogeneity, and clonal diversification is a promising approach
tailored to the genetic and functional hallmarks of the disease. The technological tools and approaches are
unique and highly innovative. The introduction of a li...

## Key facts

- **NIH application ID:** 10178258
- **Project number:** 1R01CA258226-01
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** Giannicola Genovese
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $591,326
- **Award type:** 1
- **Project period:** 2021-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10178258

## Citation

> US National Institutes of Health, RePORTER application 10178258, Investigation of the role of epithelial-mesenchymal plasticity in renal cell carcinoma (1R01CA258226-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10178258. Licensed CC0.

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