The Role of Circulating Biomarkers in the Oncological Management of Metastatic Renal Cell Carcinoma: Where Do We Stand Now?

Abstract

Renal cell carcinoma (RCC) is an increasingly common malignancy that can progress to metastatic renal cell carcinoma (mRCC) in approximately one-third of RCC patients. The 5-year survival rate for mRCC is abysmally low, and, at the present time, there are sparingly few if any effective treatments. Current surgical and pharmacological treatments can have a long-lasting impact on renal function, as well. Thus, there is a compelling unmet need to discover novel biomarkers and surveillance methods to improve patient outcomes with more targeted therapies earlier in the course of the disease. Circulating biomarkers, such as circulating tumor DNA, noncoding RNA, proteins, extracellular vesicles, or cancer cells themselves potentially represent a minimally invasive tool to fill this gap and accelerate both diagnosis and treatment. Here, we discuss the clinical relevance of different circulating biomarkers in metastatic renal cell carcinoma by clarifying their potential role as novel biomarkers of response or resistance to treatments but also by guiding clinicians in novel therapeutic approaches.

Renal Carcinoma and Angiogenesis: Therapeutic Target and Biomarkers of Response in Current Therapies

“…However, at the time of progression, patients who initially responded to sunitinib did not have increased VEGF-A levels [ 76 ]. Concerning soluble VEGF-A receptors, the decrease of sVEGFR-2 level is well described in m-ccRCC treated with antiangiogenic [ 77 ], but its association with clinical outcomes is not systematically observed. In patients with m-ccRCC treated with sunitinib, a significantly greater decrease in sVEGFR-2 levels was observed in patients with objective tumour response [ 70 , 74 ].…”

Renal Oncocytoma: The Diagnostic Challenge to Unmask the Double of Renal Cancer

“…MicroRNAs (miRNAs) are a class of small non-coding RNAs that represents a promising non-invasive cancer biomarker tool [ 202 , 203 , 204 , 205 , 206 , 207 , 208 , 209 ]. MiRNAs regulate gene expression at the post-transcriptional level by pairing to the 3′ untranslated region (UTR) of target messenger RNAs (mRNAs) through translational repression or mRNA degradation [ 210 , 211 ].…”

“…Their potential utility as predictive, diagnostic, and prognostic biomarkers in RCC patients was extensively described in previous reviews [ 207 , 208 ].…”

TIMP1 Indicates Poor Prognosis of Renal Cell Carcinoma and Accelerates Tumorigenesis via EMT Signaling Pathway

“…The main histological subtypes of RCCs are clear cell (cc) RCC (~70% of RCCs), papillary (p) RCC (10%-15% of RCCs), and chromophobe (ch) RCC (~5% of RCCs) (Morris and Latif, 2017). Cancer-specific survival rates at 5 years for the above three types of RCC are 68.9%, 87.4%, and 86.7%, respectively (Cheville et al, 2003;Cinque et al, 2021). The five-year survival rate of early-stage RCC reaches 71%-88%.…”

“…The five-year survival rate of early-stage RCC reaches 71%-88%. Still, the survival rate at 5 years of RCC plummets to only 12% when metastasis occurs according to the latest study (Leibovich et al, 2010;Cinque et al, 2021). Therefore, it is necessary to identify practical biomarkers for the early diagnosis of RCC.…”