Molecular aberrations, targeted therapy, and renal cell carcinoma: current state-of-the-art

Area of Science:

• Oncology
• Genetics
• Molecular Biology

Background:

• Renal cell carcinoma (RCC) is a common cancer in the USA.
• While most RCC cases are sporadic, 2-3% are hereditary, linked to syndromes like von Hippel-Lindau.
• Recent advances have identified key genetic mutations in sporadic RCC, including VHL, PBRM1, BAP1, and SETD2.

Purpose of the Study:

• To review the current understanding of renal cell carcinoma's molecular genetics.
• To explore how genetic insights can inform and direct therapeutic strategies for RCC.
• To highlight the association between specific gene mutations (e.g., BAP1) and disease aggressiveness.

Main Methods:

• Literature review of studies on renal cell carcinoma genetics and therapeutics.
• Analysis of common genetic mutations in sporadic and hereditary RCC.
• Overview of current targeted therapies and immunotherapies for advanced RCC.

Main Results:

• Common mutations in clear cell RCC include VHL, PBRM1, BAP1, and SETD2.
• BAP1 mutations correlate with more aggressive disease and poorer survival outcomes.
• Approved therapies include tyrosine kinase inhibitors (TKIs) and immunotherapy, but predictive genetic markers are lacking.

Conclusions:

• Understanding RCC molecular genetics is crucial for developing personalized treatment approaches.
• The absence of predictive genetic markers in current trials hinders effective therapy selection.
• Future research should focus on integrating genetic profiling to guide RCC treatment decisions.