Cancer should be a rare disease. Cancer cells defy biology by getting their energy from glucose sugar, and not oxygen—and researchers have now discovered how they do it.
Cancer cells contain a ‘powerhouse’ molecule, PI3 kinase, that acts as communicator once the disease begins. It’s part of cancer’s metabolism, and that’s why other researchers haven’t noticed it. Instead, they have been concentrating on cancer’s signalling capabilities.
But when researchers at Memorial Sloan Kettering Cancer Center started to look instead at cancer’s metabolic processes, they discovered the importance that PI3 plays in its growth. And understanding this could open the door to different cancer therapies that concentrate on the disease’s metabolism.
Scientists have had most of the pieces of the cancer puzzle for years, ever since German physicist Otto Warburg recognised that cancer cells get their energy from glucose and not oxygen, as healthy cells do. But rather than burn the sugar, cancer cells ferment it, leaving much of the energy in glucose untapped.
“PI3 kinase is a key signaling molecule that functions almost like a commander-in-chief of cell metabolism,” said lead researcher Ming Li. Once the ‘Warburg effect’ starts, PI3 kicks into life to help the cancerous cells divide and spread. “It’s a bit like giving the commander-in-chief a megaphone,” he said.
The trigger for full-blown cancer happens when an enzyme, lactate dehydrogenase A (LDHA), starts responding to PI3’s activity. In experiments with laboratory mice, Dr Li and his team discovered that T-cells without LDHA couldn’t sustain PI3 activity, and so the cancer couldn’t take hold.
And in completing the loop back to the Warburg effect, PI3 needs ATP, the cell’s energy supply—and this is the net product of the process identified by Warburg in 1930.
Focusing on LDHA activity could be the way forward for oncologists to combat cancer, the researchers add.
(Source: Science, 2021; 371: 405)