Around 1956, German physiologist Otto Warburg noticed something unusual about cancer cells in culture. They would take up vast amounts of glucose, and instead of respiring it like normal cells, they converted it into lactic acid.1
This was the first indication that cancer cells undergo what is termed “metabolic reprogramming” — either increasing, decreasing, or entirely bypassing classic metabolic pathways in order to boost tumor growth. And along with other research since, it led to the idea that cancers may produce a unique signature of altered metabolites that could be detectable in tumor tissue, or even blood or urine, and serve as prognostic or diagnostic markers for disease.
Although numerous investigations have been conducted in recent decades to identify such biomarkers, very few have proved promising enough to enter clinical studies. That is even the case for renal cell carcinoma (RCC), which some consider a metabolic disease “because there’s so much reprogramming that goes on in RCC,” said Robert Weiss, MD, professor emeritus at the department of internal medicine at the University of California, Davis.
Nevertheless, many researchers still hope to find prognostic and diagnostic biomarkers for cancer through metabolomic approaches — the quantitative analysis of metabolites.
In a recent review in Expert Review of Molecular Diagnostics, Indian researchers discussed the state of metabolomics for RCC, a disease in which they write has an unmet clinical need for prognostic and diagnostic biomarkers.2
“Metabolomics could be used for screening [people] of high genetic risk as well as family history of RCC,” wrote coauthor Ashish Gupta, PhD, assistant professor at the Center of Biomedical Research, Lucknow, India, to Cancer Therapy Advisor in an email.
Studies based on RCC tumor tissue have identified a handful of metabolic pathways that are altered. For instance, mutations affecting the VHL gene in clear cell RCC can lead the alteration of metabolic programs linked to glycolysis, fatty acid metabolism, and glutamine pathways, Dr Gupta explained.
In addition, some of Dr Weiss’s research has suggested that the amino acid tryptophan, which is normally converted to serotonin, is instead metabolized into kynurenine in RCC.3 Various other metabolites also show abnormal concentrations in RCC, some of which correlate with disease progression and therapeutic outcomes, according to the review authors.
However, many challenges lie ahead in developing these into tissue-based biomarkers that can inform diagnosis, or into prognostic blood- or urine-based biomarkers. A major difficulty is that many individual metabolite changes are often common among cancers and not specific to RCC, noted Daniel Raftery, PhD, member of the public health sciences division at the Fred Hutchinson Cancer Research Center in Seattle, Washington.