The biochemical pathways altered in cancer cells can have a variety of effects, not all of them good for the cell in question. This suggests that as such alterations accumulate in cancer cells, only those altered pathways whose consequences are in harmony with that of others allow the cell to survive and drive tumor growth. Ludwig Oxford’s Peter Ratcliffe and colleagues examined this hypothesis in renal clear cell carcinoma (RCC), a cancer driven by the constitutive activation of a key regulator of the hypoxic response, HIF. In particular, they examined the overlap between DNA-binding elements involved in the HIF pathway and variations in DNA sequences that affect cancer susceptibility. Peter and his team published in Scientific Reports in December their comparative analysis of that overlap in RCC and in other cancers in which HIF is differently activated—say, by oxygen starvation. Their findings support a “pathway tuning” model of cancer, in which precise modulation of multiple outputs of specific, activated biochemical pathways is critical to the emergence of cancer. This implies that selective pressures balance the effects of a vast network of interacting pathways during cancer development to generate a viable cancer cell and, ultimately, a tumor. This, the researchers argue, should focus attempts to identify the nature and consequences of those selective pressures.
This article appeared in the April 2020 issue of Ludwig Link. Click here to download a PDF (1 MB).