New molecular targets in non clear renal cell carcinoma: An overview of ongoing clinical trials

Area of Science:

• Oncology
• Molecular Pathology
• Cancer Therapeutics

Background:

• Non-clear cell renal cell carcinomas (nccRCCs) represent a diverse group of kidney cancers with varying histology, molecular profiles, and treatment responses.
• Current treatments for clear cell RCC (ccRCC) primarily target VEGF and mTOR pathways, significantly improving patient outcomes.
• nccRCCs may rely on alternative signaling pathways, such as the HGF/MET axis in papillary RCC, distinct from those targeted in ccRCC.

Purpose of the Study:

• To review the rationale behind using tyrosine kinase inhibitors (TKIs) and mTOR inhibitors for nccRCC treatment.
• To analyze current and emerging therapeutic strategies for nccRCC.
• To discuss future treatment perspectives for patients with nccRCC.

Main Methods:

• Literature review of current research on nccRCC classification and treatment.
• Analysis of molecular pathways implicated in nccRCC proliferation, including HGF/MET.
• Evaluation of ongoing clinical trials and therapeutic approaches for nccRCC.

Main Results:

• nccRCCs exhibit significant heterogeneity, necessitating tailored treatment approaches.
• The HGF/MET pathway is a potential therapeutic target in specific nccRCC subtypes.
• Various targeted therapies, including TKIs, mTOR inhibitors, MET antagonists, and immunotherapy, are under investigation for nccRCC.

Conclusions:

• Targeted therapies offer promising avenues for nccRCC treatment, moving beyond ccRCC-specific strategies.
• Understanding the molecular drivers of different nccRCC histotypes is crucial for effective therapy selection.
• Future research should focus on personalized treatment strategies based on nccRCC molecular characteristics and pathway activation.