# Dynamics of protein kinase CK2 signaling in prostate cancer pathogenesis

> **NIH VA I01** · MINNEAPOLIS VA  MEDICAL CENTER · 2021 · —

## Abstract

Prostate cancer (PCa) is one of the major health issues for the aging Veterans population warranting
investigations to further advance knowledge of the disease pathobiology and benefit PCa patients, which accords
with the VA Healthcare mission. In this context, our focus has been centered on delineating the functions of the
pro-survival and cancer-addictive protein kinase CK2 in PCa pathobiology and therapy, resulting in significant
ground-breaking contributions over time. Protein kinase CK2 (formerly casein kinase 2 or II) was originally
studied by us in relation to prostate biology, and CK2 is now recognized as one of the “master regulators” of
diverse functions in normal and malignant cells. Higher relative CK2 levels and activity correspond with
aggressive PCa disease, and CK2 proteins localize preferentially to the nucleus in PCa tumors. Crosstalk
between androgen receptor (AR), NFκB p65 and CK2 is demonstrated by us and others. Anti-CK2 treatments
cause loss of AR and NFκB p65, with cell death ensuing regardless of the androgen and drug sensitivity of PCa
cells. Currently, androgen deprivation therapy is the standard of care for many PCa patients; however, resistance
to androgen deprivation develops with progression from castration-sensitive to castration-resistant PCa (CRPC).
Response to next generation anti-androgenic approaches (Abiraterone and/or Enzalutamide used ±
chemotherapy and more recently immunotherapy) is also temporary with development of resistance to these
therapies so that the mortality rates from metastatic CRPC (mCRPC) remain high. Thus, there is critical need
for identification of strategies to maintain drug response and prevent disease progression. Our new data show:
(1) PCa cells grown under multiple conditions that exert androgen pathway stress exhibit elevated CK2 levels;
(2) CK2 protein levels are higher in multiple PCa xenograft tumor models in castrated vs. testes-intact mice; (3)
CK2α mRNA is detected in pre-prostatectomy PCa patient serum, and the levels are significantly increased in
abiraterone-treated PCa patients serum; (4) High CK2 protein levels in tumors at prostatectomy correlate
significantly with faster progression to metastatic disease; and (5) Inhibition of CK2 kills Abiraterone- and
Enzalutamide-resistant PCa cells, and is synergistic with Abiraterone. These exciting novel observations prompt
the hypothesis that induction of CK2 and the subsequent impact on AR and NFκB pathways promotes therapy
resistance to current AR targeting therapies. We propose to determine molecular mechanisms involved in CK2
promotion of androgen pathway therapy resistance, and establish how CK2 functions as a driving factor for PCa
disease progression. Specific aim 1 will test the hypothesis that suppression of CK2 activity will delay or
prevent PCa progression or reverse resistance to androgen pathway targeting, and is designed to examine the
effect and mechanism of the clinical grade anti-CK2 small molecule inhibitor CX-4...

## Key facts

- **NIH application ID:** 10121377
- **Project number:** 1I01BX005091-01A1
- **Recipient organization:** MINNEAPOLIS VA  MEDICAL CENTER
- **Principal Investigator:** Khalil Ahmed
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2021-01-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10121377

## Citation

> US National Institutes of Health, RePORTER application 10121377, Dynamics of protein kinase CK2 signaling in prostate cancer pathogenesis (1I01BX005091-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10121377. Licensed CC0.

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