Researchers are zeroing in on microRNAs (miRNAs) circulating in the bloodstream as biomarkers for the detection and diagnosis of renal cell carcinoma (RCC), and are increasingly hopeful of unlocking their potential as targeted therapies for combatting the disease.
“We know what genes are responsible for RCC, or at least many cases of RCC,” said Farhad R. Danesh, MD, chief of the division of nephrology at MD Anderson Cancer Center in Houston, Texas. “We have more or less well established what should be the targets. It is just a question of how can we change the behavior of these genes. And one way to do that is through manipulating the miRNAs that regulate these genes.”
As a paper published in June 2017 noted: “aberrant expression of miRNAs is an established feature of human malignancy and has been associated with oncogenesis and tumor progression…Given their ease of access and stability, circulating miRNAs show great promise as novel minimally invasive biomarkers.”1
Every year, more than 337,000 new cases of renal cancer are diagnosed worldwide and more than 143,000 people die from the disease.
Caught early, RCC is highly treatable, with nephrectomy as the standard first-line treatment. The American Cancer Society reports a 5-year relative survival rate of 93% for cases in which the cancer has not spread beyond the kidney at the time of diagnosis.2
The study’s authors note, however, that “early-stage RCC is typically asymptomatic, frequently leading to delayed diagnosis, often at advanced stages with limited therapeutic options.”
According to a 2015 meta-analysis, about 20% to 30% of “patients have metastatic disease at the time of diagnosis, and another 30% who undergo curative surgery for localized RCC develop metastasis during follow-up.”3
While therapies targeting the vascular endothelial growth factor (VEGF) pathway can extend the lives of patients with advanced disease, researchers continue to evaluate diagnostic tools that allow them to catch signs of RCC earlier.
“At present,” the authors of a 2015 integrated profiling analysis wrote, “biomarkers for early detection and follow-up of RCC are not available, which accounts for late diagnosis and subsequent poor prognosis. Therefore, searching for novel tumor biomarkers that enable the early detection and precise prognosis for patients with RCC has become a focus of basic and clinical RCC research.”4
A signature miRNA or group of miRNAs might serve that purpose, Dr Danesh said.
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Since they were first identified in 1993, miRNAs have been shown to have a role in biological functions ranging from cellular proliferation and cell cycle control to apoptosis, angiogenesis, tissue invasion, and metastasis, “suggesting that they have a vital role in the development and progression of different cancers,” the authors of the meta-analysis wrote. “Correspondingly, [miRNAs] have also been shown to have prognostic significance in several tumor types, including colon, lung, breast, and ovarian cancer.”
The significance of circulating miRNA in RCC is not as clear cut.