Targeting the Y-box Binding Protein-1 Axis to Overcome Radiochemotherapy Resistance in Solid Tumors

Area of Science:

• Oncology
• Molecular Biology
• Cancer Research

Background:

• Y-box binding protein-1 (YB-1) is a multifunctional protein highly expressed in human solid tumors.
• YB-1 regulates critical cancer hallmarks including DNA damage response, gene transcription, and tumor stemness.

Purpose of the Study:

• To review the prosurvival role of YB-1 in DNA damage repair and cancer stemness.
• To highlight the clinical evidence correlating YB-1 expression with treatment outcomes after radiochemotherapy (RCT).
• To summarize YB-1 signaling, posttranslational modifications, and therapeutic targeting strategies, especially in combination with RCT.

Main Methods:

• Literature review focusing on YB-1's role in cancer progression and treatment response.
• Analysis of YB-1's involvement in DNA damage response and cancer stemness pathways.
• Summary of current research on targeting YB-1 and its signaling cascades.

Main Results:

• YB-1 exhibits a prosurvival effect, enhancing DNA damage repair and promoting cancer cell stemness.
• Clinical data show an inverse correlation between YB-1 expression and treatment outcomes in solid tumors following RCT.
• p90 ribosomal S6 kinase and AKT are key kinases activating YB-1, suggesting them as therapeutic targets.

Conclusions:

• Molecular targeting of YB-1, especially in combination with RCT, is a potential strategy to overcome treatment resistance in solid tumors.
• Understanding YB-1's functions and regulation is crucial for developing effective cancer therapies.
• Further research into YB-1 posttranslational modifications and signaling pathways may reveal novel therapeutic targets.