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Updated: Jun 10, 2026
The Use of Reverse Phase Protein Arrays RPPA to Explore Protein Expression Variation within Individual Renal Cell Cancers
Published on: January 22, 2013
Genomic profiling and molecular characterization of non-clear cell renal cell carcinoma: a narrative review from a
Gaetano Pezzicoli1, Vittoria Musci1, Federica Ciciriello1
1Department of Interdisciplinary Medicine, University of Bari "Aldo Moro," Bari, Italy.
Abstract:
While the clear-cell renal cell carcinoma (ccRCC) treatment has undergone several paradigm shifts in recent years, the non-clear cell renal cell carcinoma (nccRCC) therapeutic approach has yet to be extensively investigated and improved. The WHO 2022 classification of renal neoplasms redefined the most common nccRCC subtypes (papillary and chromophobe RCC) and introduced the molecularly defined RCC class, which is a first step in the direction of better molecular profiling of nccRCC. We reviewed the literature data on known genomic alterations of clinical interest in nccRCC and discussed their potential role in guiding therapeutic choices in each nccRCC entity. Among the alterations discussed, we focused on the ones that could be treated with already available drugs, such as MET-driven papillary RCC, mechanistic target of rapamycin altered chromophobe RCC, anaplastic lymphoma kinase-rearranged RCC, and fumarate-hydratase deficient RCC. Furthermore, we focused on the currently ongoing clinical trials and further evidence for all the other entities, such as SMARCB1-deficient RCC, TFE3 and transcription factorEB (TFEB)-altered RCC, and Elongin C (ELOC)-mutated RCC. The vast heterogeneity of nccRCC does not allow a one-size-fits-all solution; therefore, molecular characterization is the path toward effective therapies and fully personalized medicine for these entities.
Insights
Non-clear cell renal cell carcinoma (nccRCC) treatment lags behind clear-cell RCC. Molecular profiling of nccRCC subtypes is key to developing targeted therapies and personalized medicine.
Area of Science:
- Oncology
- Genetics
- Translational Medicine
Background:
- Clear-cell renal cell carcinoma (ccRCC) treatments have advanced, but non-clear cell RCC (nccRCC) therapies remain less explored.
- The WHO 2022 classification advances nccRCC subtyping and molecular profiling.
Purpose of the Study:
- To review genomic alterations in nccRCC with clinical relevance.
- To discuss the potential of these alterations in guiding therapeutic choices for nccRCC entities.
- To highlight available and emerging treatments based on molecular profiling.
Main Methods:
- Literature review of genomic alterations in nccRCC.
- Analysis of potential therapeutic targets and available drugs.
- Examination of ongoing clinical trials for nccRCC.
Main Results:
- Identified treatable alterations in MET-driven papillary RCC, mTOR-altered chromophobe RCC, ALK-rearranged RCC, and FH-deficient RCC.
- Summarized ongoing trials for SMARCB1-deficient RCC, TFE3/TFEB-altered RCC, and ELOC-mutated RCC.
Conclusions:
- nccRCC is highly heterogeneous, precluding a one-size-fits-all approach.
- Molecular characterization is essential for effective, personalized nccRCC therapies.
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