Researchers have found that deadly kidney cancers can be identified by assessing their evolutionary path, which is different for distinct types. There are three evolutionary paths that kidney cancer follows; one never becomes aggressive, while one forms serious tumors that can spread cancer through the body. This work could help develop better diagnostics and improve personalized medicine; it has been reported in Cell over three publications.
"The outcomes of patients diagnosed with kidney cancer vary a great deal - we show for the first time that these differences are rooted in the distinct way that their cancers evolve,” said lead author Dr. Samra Turajlic, Cancer Research UK clinician scientist at the Francis Crick Institute and consultant oncologist at The Royal Marsden.
In the two of the studies, the TRACERx Renal team from the Francis Crick Institute, UCL, The Royal Marsden NHS Foundation Trust, and Guy's and St Thomas' NHS Foundation Trust, assessed the genetic events that led to the growth of tumors in 100 kidney cancer patients.
The research has shown that in one type of aggressive kidney cancer, there are rapid bursts of damage that impact large regions of the genome, which happens early on in its development. Such tumors then have all the ammunition they need to spread, even before the kidney tumor is detected.
A second evolutionary path creates a kidney cancer that can’t grow rapidly. The third and final path of evolution the scientists found in these cancers are tumors that are damaged gradually over time (as opposed to a sudden burst). Tumors like this often spread but only to one other place, and are made up of cells with many different characteristics.
"Knowing the next step in cancer's evolutionary trajectory could tailor the treatment choice for individual patients in the next decade. For instance, patients with the least aggressive tumors could be spared surgery and monitored instead, and those with gradually evolving tumors could have the primary tumor surgically removed even after it has spread,” noted Turajlic. “Unfortunately, surgery is unlikely to halt the 'born to be bad' tumors that are aggressive at the earliest stage, highlighting the need for early detection programs.”
Two biomarkers were also identified that drive cancer metastasis, which can help clinicians identify patients that are at risk.
In the third study by TRACERx researchers are colleagues at Wellcome Sanger Institute in Cambridge, scientists learned that kidney cancer can start in childhood; it may take 50 years before anyone detects the primary tumor. This work could be an excellent opportunity for developing early interventions.
"We can now say what the initiating genetic changes are in kidney cancer, and when they happen. What is remarkable is that the hallmark genomic event that characterizes kidney cancer takes place on average 40 to 50 years before the cancer is diagnosed. These first seeds are sown in childhood or adolescence - knowing the sequence of events and their timings opens opportunities for early intervention,” said corresponding author Dr. Peter Campbell, of the Wellcome Sanger Institute, said:
"For years, we've grappled with why patients with seemingly very similar diagnoses have such vastly different outcomes, some dying very quickly and some surviving for decades after treatment. These ground-breaking studies help us unravel this conundrum,” noted Sir Harpal Kumar, Cancer Research UK's chief executive.
"When Cancer Research UK scientists first revealed that the genetic makeup of cancers evolves over time, helping tumors to become resistant to treatments, we were faced with a monumental challenge of how to tackle this complexity. Now we know that there are rules in this complexity, and we could use these rules to help choose the best treatments, and potentially to diagnose some cancers much earlier."
Sources: Science Daily via The Francis Crick Institute, Cell Turajlic et al 2018, Cell Turajlic et all 2018, Cell Mitchell at al 2018
