CK2 in triple-negative breast cancer: oncogenic signaling networks and emerging CK2 inhibitor-based combination...

Area of Science:

• Oncology
• Molecular Biology
• Cancer Therapeutics

Background:

• Triple-negative breast cancer (TNBC) is aggressive, heterogeneous, and resistant to standard treatments, leading to poor outcomes.
• Casein kinase 2 (CK2), a serine/threonine kinase, is aberrantly activated in TNBC, driving oncogenic pathways like proliferation, DNA repair, and epithelial-to-mesenchymal transition (EMT).
• CK2 also influences tumor redox balance and immune evasion by stabilizing PD-L1, contributing to treatment resistance and tumor progression.

Purpose of the Study:

• To investigate the multifaceted role of aberrant CK2 signaling in TNBC.
• To evaluate the therapeutic potential of CK2 inhibitors, particularly in combination therapies, for overcoming TNBC treatment resistance.

Main Methods:

• Review of preclinical and clinical research on CK2 signaling in TNBC.
• Analysis of CK2's involvement in oncogenic pathways, DNA repair, EMT, and immune modulation.
• Examination of synergistic effects of CK2 inhibitors with chemotherapy, targeted agents, and immunotherapies.

Main Results:

• CK2 overactivation promotes TNBC growth, metastasis, and resistance to therapies by regulating multiple survival and oncogenic pathways.
• Pharmacological inhibition of CK2 disrupts these pathways, enhancing TNBC cell susceptibility to treatments.
• CK2 inhibitors demonstrate synergistic anticancer effects when combined with chemotherapy, PI3K/AKT/mTOR inhibitors, PARP inhibitors, and immunotherapies by suppressing compensatory survival mechanisms.

Conclusions:

• Aberrant CK2 signaling is a critical driver of TNBC progression and treatment resistance.
• CK2 inhibitors represent a promising therapeutic strategy for TNBC, especially in combination regimens.
• Next-generation CK2 inhibitors offer a novel approach to improve treatment efficacy and clinical outcomes for TNBC patients.