# Identifying and Characterizing Therapeutic Targets in Adrenal Cancer

> **NIH NIH K08** · UNIVERSITY OF COLORADO DENVER · 2021 · $209,995

## Abstract

Project Summary
Adrenocortical carcinoma (ACC) is an aggressive, fatal cancer with five-year survival less than 35%. Surgery
remains the only chance of a cure; however, many tumors are unresectable at time of presentation. Lack of
human ACC research models has significantly limited progress in the field. Recent establishment of Multi-
Disciplinary Adrenal Tumor group at University of Colorado (CU) provides an ideal platform for a collaborative
research to advance the field. We have recently established the first new human ACC cell lines and ACC
patient derived xenografts (PDX). In parallel, using bioinformatic analyses of published databases, I have
identified novel kinases dysregulated in ACC. My initial focus is on maternal embryonic leucine zipper kinase
(MELK) which is upregulated 5-25-fold in 40-50% of ACC and low or absent in normal adrenal tissue.
Increased MELK expression is correlated with a shorter survival in patients with ACC. Preliminary data
support my hypothesis that MELK confers an oncogenic signal by increasing tumorigenesis, proliferation and
survival in vitro. The goals for this proposal is to use our ACC models to dissect the mechanism and functional
significance of dysregulated kinases such as MELK in ACC. Studies will dissect the functional role of MELK
and its downstream targets in our newly developed ACC cell lines; identify potential escape mechanisms from
MELK inhibition; and examine whether inhibiting MELK with or without blocking escape pathways leads to
decrease tumor growth in our new PDX models. My ultimate career goal is to become an independent
physician scientist in the area of endocrine neoplasia with a focus in ACC. Towards this goal, my mentored
career development program will allow me: 1) to acquire new technical laboratory skills in in vitro and in vivo
assays; 2) to expand my training in bioinformatics using genomic and proteomic platforms 3) to expand training
into future phase I studies 4) to promote integration of research findings to clinical practice. This proposal
includes a strong and diverse mentoring team including Dr. Wierman with extensive mentoring experience and
expertise in tumor biology focused on endocrine neoplasia, Dr. Schweppe, a signal transduction expert with
extensive experience in genomic and proteomic approaches in tumor biology and Dr. Leong who integrates
research from PDX in GI cancer to Phase I studies. They will ensure expertise in experiment design, new
laboratory, and clinical research skills, critical data analysis and advice about career development.
Collaborators will provide hands on additional training in bioinformatics, as well as development of cutting edge
research techniques and models. In addition Dr. Hammer, University of Michigan, an internationally renowned
expert in ACC, will provide mentorship to ensure that I am integrated into the ACC community by developing
collaborations which will amplify my work. The outcome of these studies will have a significant impact ...

## Key facts

- **NIH application ID:** 10244906
- **Project number:** 5K08CA222620-04
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Katja KISELJAKVASSILIADES
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $209,995
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10244906

## Citation

> US National Institutes of Health, RePORTER application 10244906, Identifying and Characterizing Therapeutic Targets in Adrenal Cancer (5K08CA222620-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10244906. Licensed CC0.

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