# Protein kinase CK2 in prostate cancer progression and clinical potential for therapy

> **NIH VA I01** · MINNEAPOLIS VA  MEDICAL CENTER · 2024 · —

## Abstract

Protein kinase CK2 (CK2) regulates several biological features that are hallmarks of cancer. Its
consistent dysregulation in various cancers has led to the suggestion that it is a master regulator
of malignant cells, further highlighted by its potential as a therapy target. This CSR&D research
proposal is designed to investigate the mechanism of function of CK2 in prostate cancer (PCa)
pathobiology; specifically, to define how nuclear elevation of CK2 is involved in transcriptional
mechanisms of castration resistant PCa (CRPC) tumor signaling and relation to progression-free
survival (PFS) in CRPC patients. Our preliminary data demonstrate the association of androgen
axis therapies with elevation of intra- and extra-cellular CK2 levels and PCa progression,
prompting our current focus on roles for CK2 in CRPC transcriptional regulation. Our hypothesis
is that elevation of CK2 levels caused by androgen axis therapies enables treatment resistance
through altered transcriptional programming and CK2-associated nuclear protein complexes.
Further, higher tumor-released CK2 mRNA in PCa patient blood results in worse progression-free
survival.
Two specific aims (Aims 1 and 2) address the basic science mechanism questions in the project
while Aim 3 links the expression of CK2 in CRPC disease to patient outcomes.
Specific Aim 1: determine how elevated CK2 activity alters the AR-related transcriptional program
under androgen axis treatment stress and develop a CK2 gene signature to assess CK2 activity
in clinical datasets.
Specific Aim 2: elucidate CK2-regulated nuclear protein interactions and their contribution to
enhanced CRPC survival under androgen axis treatment stress.
Specific Aim 3: in a prospective study, measure CK2 mRNA serum levels in a CRPC cohort and
correlate baseline CK2 levels with PFS. This aim has two further sub-studies. The first is a
prospective study to compare CK2 mRNA levels in serum of patients pre- and post-prostatectomy.
The second is a retrospective study to correlate CK2 mRNA and protein in metastatic CRPC
biopsies with CK2 mRNA in matching patient serum.
The mechanisms of how elevated nuclear CK2 is involved in PCa have remained unclear thus
far. The present investigations will provide, for the first time, mechanistic data related to CK2-
regulated transcriptional programming and nuclear protein interactions in CRPC disease. These
studies will also provide the first novel proof-of-concept evidence for association of CK2 serum
mRNA with tumor levels and disease progression, providing cross-validation between patient and
model data and the scientific basis for including a drug to block CK2 activity. There is a direct path
to clinical translation of this work by incorporating into PCa treatment a clinical grade inhibitor of
CK2 (CX-4945/Silmitasertib) that is being pursued for phase II clinical trials in other cancers. High
incidence of PCa in the VA and military personnel warrants identification of novel and effective
strategies...

## Key facts

- **NIH application ID:** 10805719
- **Project number:** 1I01CX002701-01A1
- **Recipient organization:** MINNEAPOLIS VA  MEDICAL CENTER
- **Principal Investigator:** Mark A. Klein
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2024-05-01 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10805719

## Citation

> US National Institutes of Health, RePORTER application 10805719, Protein kinase CK2 in prostate cancer progression and clinical potential for therapy (1I01CX002701-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10805719. Licensed CC0.

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