In particular, here we report on the identification of CK2-TN03, a CK2 inhibitor showing greater selectivity and cellular efficacy than silmitasertib, the only available clinical grade CK2 inhibitor with orphan status for cholangiocarcinoma and in clinical trials for medulloblastoma...Accordingly, neuroblastoma cells persistently stall in mitosis before going to apoptosis. Finally, CK2-TN03 does not affect noncycling cells and significantly reduces tumor growth in mice xenografts without any apparent toxicity.

CX-4945 (silmitasertib) is being tested in several early-phase clinical trials against adult and pediatric cancers. These preclinical results support the use of CX-4945 in combination with VEN to overcome resistance to apoptosis and re-sensitize VR-AML to chemotherapy.

HERPUD1 silencing reduced TNBC cell proliferation, migration, and invasion while enhancing doxorubicin (DOX) cytotoxicity, in both 2D and 3D cell culture models. Strikingly, inhibition of CK2 with CX-4945 not only reduced HERPUD1 levels but also increased the sensitivity of BC cells to DOX. HERPUD1-S59D phosphomimetic mutants showed opposite effects.Our findings establish HERPUD1 as a key mediator of PA-driven aggressiveness, dependent on the lipid-handling capacity of TNBC cells and reveals a mechanistic to lipid stress and tumor progression.

P1/2, N=21, Terminated, Pediatric Brain Tumor Consortium | N=66 --> 21 | Trial completion date: Feb 2030 --> Aug 2025 | Active, not recruiting --> Terminated | Trial primary completion date: Mar 2026 --> Aug 2025; The decision to permanently close PBTC-053 was made following communication from the NCI that the PBTC grant will not be extended beyond March 31, 2026.

CX-4945 showed synergistic cytotoxic activity with Temozolamide and Irinotecan. CX-4945 is currently being tested in a Phase 1 study to evaluate the safety and tolerability in combination with chemotherapy for the treatment of pediatric colloid tumors, including Ewing sarcoma. The preclinical studies reported here support the clinical studies evaluating the efficacy of CX-4945 for the treatment of Ewing sarcoma.

CK2α is significantly overexpressed in the tumor tissue of female CRC patients and shows a strong age-related correlation. These findings suggest a sex- and age-specific regulatory mechanism potentially influenced by estrogen signaling or menopause. Such dimorphisms underscore the need for sex-specific strategies in CRC biomarker development and therapy.

P1/2, N=66, Active, not recruiting, Pediatric Brain Tumor Consortium | Trial primary completion date: Dec 2029 --> Mar 2026

P1/2, N=66, Active, not recruiting, Pediatric Brain Tumor Consortium | Recruiting --> Active, not recruiting

CK2 may be a potential therapeutic target and could contribute to the pathophysiology of AD. However, these findings should be validated by further studies.

P1, N=25, Completed, Senhwa Biosciences, Inc. | Active, not recruiting --> Completed

P2, N=45, Terminated, Senhwa Biosciences, Inc. | N=136 --> 45 | Recruiting --> Terminated; The trial ended early in March 2025 due to changes in disease epidemiology, affecting patient availability and recruitment feasibility.

Conversely, CK2 depletion or treatment with a CK2 inhibitor reversed these effects. Our findings reveal a novel mechanism by which the CK2/PD-L1/EGFR pathway promotes tumor progression.