Ribosomal protein S6: A Novel biomarker in the molecular era of breast cancer diagnosis and prognosis

• Author Details:   
• Anmol Mahani ^*
• Viney Kumar
• Vipul Nautiyal
• Mansi Barthwal

---

Introduction: Carcinomas continue to be a significant global health challenge, with an estimated 20 million new cases and 9.7 million deaths reported world-wide, in 2022. In India, the carcinoma burden has been rising, with breast carcinoma being the leading cause of cancer incidence and mortality among women, accounting for 13.5% of new cancer cases and 10% of carcinoma related deaths in 2020. This increasing incidence under-scores the need for more precise prognostic markers to improve risk assessment and therapeutic targeting. The shift toward molecular-oncology has transformed cancer management, moving from conventional histopathology to biomarker-driven approaches. Established markers such as ER, PR, HER2 and Ki-67 guide treatment strategies; however, new biomarkers are needed to enhance risk assessment and therapeutic targeting. Ribosomal protein s-6 (RIBPS-6), a downstream effector of the PI3K, AKT, m-TOR pathway, has emerged as a potential candidate. Recent studies suggest that phosphorylated RIBPS-6 (pS6) at Ser240/244 is linked to increased tumor proliferation and recurrence in breast cancer, making it a promising prognostic marker.
Aims and Objectives: This review aims to analyse the role of RIBPS-6 as a prognostic biomarker in breast cancer by synthesising data from multiple studies. It focuses on:  1. Understanding the mechanistic role of RIBPS-6 in breast cancer; 2. Evaluating its clinical significance in prognosis and recurrence prediction; 3. Comparing RIBPS-6 with other emerging biomarkers in breast cancer.
Materials and Methods: A systematic review was conducted across PubMed, Scopus and Web of Science databases, focusing on studies published up to March 2025. The search terms included "RIBPS-6," "phosphorylated RIBPS-6," "breast cancer," "recurrence," and "prognostic marker." Inclusion criteria encompassed studies that investigated RIBPS-6 expression or phosphorylation in breast cancer tissues and analysed its association with clinical outcomes, particularly recurrence rates. A total of 15 studies met these criteria and were included in the review.
Results: Recent studies demonstrate that phosphorylated RIBPS-6 (pS6) at Ser240/244 is significantly associated with poor recurrence-free survival in hormone receptor-positive, HER2-negative breast cancer patients. RIBPS-6 expression correlates with the PI3K, AKT, m-TOR pathway, which is frequently dysregulated in breast cancer, making it a potential therapeutic target.
Conclusion: RIBPS-6 represents a promising biomarker in the molecular era, with potential applications in breast cancer prognosis and treatment planning. Future research should focus on large-scale clinical validation and the development of targeted inhibitors to improve patient outcomes.

Keywords: Ribosomal protein S6, Breast cancer, Biomarker, PI3K, AKT, m-TOR Pathway, Prognostic marker, Molecular-oncology.