Dual-Targeting AKT2 and ERK in cancer stem-like cells in neuroblastoma

Area of Science:

• Oncology
• Molecular Biology
• Pediatric Cancer Research

Background:

• Neuroblastoma is a challenging pediatric solid tumor, especially in refractory and relapsing cases.
• Diverse molecular profiles characterize treatment-resistant neuroblastomas.
• AKT2 has a known role in neuroblastoma tumorigenesis.

Purpose of the Study:

• To investigate if targeting AKT2 can inhibit signaling pathways in chemo- and radiation-resistant neuroblastoma cancer stem-like cells.
• To evaluate the efficacy of AKT2 and MAPK pathway inhibitors in resistant neuroblastoma cells.

Main Methods:

• Utilized cisplatin (CDDP)- and radiation-resistant neuroblastoma cell models.
• Administered specific inhibitors: CCT128930 (AKT2 inhibitor) and PD98059 (MEK inhibitor).
• Assessed cell proliferation, angiogenesis, migration, sphere-forming capacity, and stem cell marker expression (CD133, SOX2, ALDH, Nestin, Oct4, Nanog).

Main Results:

• Enhanced AKT2/mTOR and MAPK signaling pathways were identified in resistant neuroblastoma cells.
• Inhibitors decreased proliferation, angiogenesis, and migration in resistant cells.
• Resistant cells exhibited increased sphere formation and stem cell marker expression, which were sensitive to the inhibitors.

Conclusions:

• Targeting AKT2 and MAPK pathways is a promising strategy against chemo- and radiation-resistant neuroblastoma.
• Resistant cancer stem-like cells are crucial for understanding therapeutic resistance mechanisms.
• Findings may lead to novel treatments and improved outcomes for neuroblastoma patients.