Renal cancer subtypes: Should we be lumping or splitting for therapeutic decision making?

Abstract

The treatment of advanced renal cell carcinoma has posed a challenge for decades, in part because of common themes related to intrinsic resistance to cytotoxic chemotherapy, and the obscure biology of these cancer types. Forward movement in the treatment of the renal cell carcinomas can thus be approached in two ways: splitting the tumor types along histologic and molecular features, in the hopes of coupling highly precision-focused therapy on a subset of disease with most potential for benefit, or lumping the various biologies and histologies together, in order to carry the rarer renal cell carcinoma types with more common disease. The former strategy satisfies our desire for customized precision in treatment delivery, while the latter strategy allows us to offer a wider therapeutic menu in a set of diseases we are continuing to learn about on a physiologic and molecular level.

Predictors of Survival Outcomes in Non-Metastatic Renal Cell Carcinoma in Latin America and Spain: A Multicentric Analysis

“…Interestedly, we detected a high proportion of chromophobe RCC in this population (16%). The literature usually reports a proportion between 6% and 10% [40]. Moreover, the survival rates of chromophobe RCC were better, which is consistent with this histologic subtype.…”

Renal Cell Tumors: Understanding Their Molecular Pathological Epidemiology and the 2016 WHO Classification

“…One copy of VHL is either mutated or silenced in 90% of sporadic CCRCCs, whereas another copy is typically lost through 3p deletions, according to the comprehensive molecular profiling of CCRCCs by The Cancer Genome Atlas (TCGA) [ 2 ]. The biallelic loss of VHL allows for the inappropriate stabilization of hypoxia-inducible factors (HIFs), which results in a proangiogenic gene expression signature that is critical to the carcinogenesis of CCRCC [ 29 , 30 ]. According to the TCGA, CCRCCs are characterized by recurrent mutations in the PI3K/AKT/MTOR pathway (a potential therapeutic target), mutations in SETD2 (associated with widespread DNA hypomethylation), and mutations involving the SWI/SNF chromatin remodeling complex ( PBRM1 , ARID1A , and SMARCA4 ).…”

Extracellular miR-224 as a prognostic marker for clear cell renal cell carcinoma

“…Renal cell carcinoma (RCC) accounts for 2% of all cancer diagnoses and cancer deaths worldwide [ 1 ]. Approximately 75% of RCCs are clear cell RCCs (ccRCCs), and ccRCC is the major cause of cancer-specific mortality (CSM) [ 2 , 3 ]. Localized RCC can be treated with partial or radical nephrectomy.…”