Translating RB1 predictive value in clinical cancer therapy: Are we there yet?

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• The retinoblastoma (RB1) gene, identified as the first tumor suppressor, plays a critical role in cell cycle regulation.
• RB1 loss-of-function and pathway alterations are prevalent in human cancers, often correlating with prognosis.
• RB1 status significantly impacts cellular responses to various stimuli and therapeutic interventions.

Purpose of the Study:

• To provide an overview of RB1's role in response to diverse anti-cancer therapies.
• To review the predictive value of RB1 status in clinical practice.
• To discuss emerging non-canonical RB1 functions influencing treatment outcomes.

Main Methods:

• Literature review of studies on RB1 and therapeutic responses.
• Analysis of RB1's role in conventional cytotoxic/cytostatic treatments.
• Review of RB1's predictive value in response to targeted therapies (e.g., CDK4/6 inhibitors, kinase inhibitors) and immunotherapy.

Main Results:

• RB1 status is a crucial determinant of cell response to both traditional and modern anti-cancer strategies.
• The predictive value of RB1 is underutilized due to functional complexity, context-dependency, and technical challenges.
• RB1 influences outcomes across various cancer types, including hormone-dependent cancers.

Conclusions:

• RB1's complex role necessitates further investigation for optimal clinical application.
• Understanding RB1's canonical and non-canonical functions is vital for predicting and improving anti-cancer treatment efficacy.
• Integrating RB1 status into clinical decision-making holds potential for personalized cancer therapy.