# NON-INVASIVE PHYSIOLOGIC PREDICTORS OF AGGRESSIVENESS IN RENAL CELL CARCINOMA

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2024 · $331,538

## Abstract

Abstract
The routine use of cross-sectional imaging has resulted in a dramatic increase in the age-adjusted incidence of
renal cell carcinoma (RCC) over the last decades. However, this has not translated into a decrease in cancer
specific deaths, which suggests over treatment of potentially indolent renal tumors. Thus, active surveillance
(AS) of RCC is now accepted as a management option for renal tumors, particularly in patients with
comorbidities. Although AS in larger tumors has been reported to be safe (i.e. very low risk of metastasis), the
natural history of these tumors remains unknown and percutaneous biopsies may be limited in assessing tumor
grade due to intrinsic heterogeneity. Tumor angiogenesis and lipogenesis have been correlated with prognosis
and metastatic potential in clear cell RCC (ccRCC), the most common and aggressive type of RCC. Inactivation
of the VHL gene, HIF upregulation, and VEGF over-expression form the molecular basis of the enhanced
angiogenesis associated with ccRCC. More recently, progress has been made in recognizing the distinct role of
HIF-1 and HIF-2 transcription factors in tumor progression and inhibition of HIF-2, the main driver of
angiogenesis, is now been tested in humans. Similarly, upregulation of lipogenic enzymes has been recognized
as an aggressive metabolic phenotype in ccRCC. Arterial spin labeling (ASL) is a magnetic resonance imaging
(MRI) method for measuring blood flow by manipulating the signal from inflowing arterial blood. ASL blood flow
correlates tightly to vascularity in ccRCC. Dixon-based techniques have been extensively validated for
quantification of hepatic lipids. Diffusion weighted imaging (DWI) provides an indirect non-invasive estimate of
tumor cellularity. We seek to identify cellularity, vascular, and lipid MRI measures in ccRCC in vivo that correlate
to spatially-co-localized molecular alterations promoting angiogenesis and lipogenesis and predict aggressive
behavior. The spatial co-localization of various tissue-based analyses with in vivo alterations in tumor perfusion
and lipogenesis may help develop more robust imaging biomarkers to predict the biologic behavior of ccRCC. If
successful, these imaging biomarkers will be immediately applicable to clinical practice and will help selecting
patients for active surveillance thus decreasing the number of unnecessary surgeries.

## Key facts

- **NIH application ID:** 10774263
- **Project number:** 5R01CA154475-11
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Yin Xi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $331,538
- **Award type:** 5
- **Project period:** 2011-09-15 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10774263

## Citation

> US National Institutes of Health, RePORTER application 10774263, NON-INVASIVE PHYSIOLOGIC PREDICTORS OF AGGRESSIVENESS IN RENAL CELL CARCINOMA (5R01CA154475-11). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10774263. Licensed CC0.

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