# On why cancer cells require a great amount of glucose

## TL;DR

Cancer cells consume large amounts of glucose to maintain pH balance and produce nucleotides, which are essential for their survival and growth.

## Contribution

This study reveals that glucose is primarily used for acid-base regulation and nucleotide synthesis, not directly for cell division.

## Key findings

- Cancer cells use glucose to produce H+ ions to stabilize cytosolic pH and prevent cell death.
- Nucleotide biosynthesis is the main acidifying pathway and consumes the largest glucose metabolic flux in most cancers.
- Synthesized nucleotides, rather than glucose itself, drive cancer cell proliferation.

## Abstract

The traditional thinking has been that cancer cells require a great amount of glucose to support their rapid growth, but the reality may be different. We have previously demonstrated that all cancer cells in The Cancer Genome Atlas harbor persistent Fenton reactions in their cytosol, which generate OH− and ultimately kill the cells by alkalosis if not neutralized timely. Here, we present data to show that (1) cancer cells uptake large amounts of glucose to produce sufficient levels of H+ions to keep the cytosolic pH stable, hence keeping the cells viable; (2) de novo nucleotide biosynthesis represents the predominant acidifying pathway and gets on average the largest allocation of glucose metabolic flux among the 19 cancer types investigated; and (3) although the H+ions produced by nucleotide biosynthesis and other acidifiers keep the cells alive, the synthesized nucleotides drive cancerous cell proliferation. Taken together, it is not that cancerous cell division requires high levels of glucose imports, instead it is the life‐saving nucleotide syntheses that drive cell division. Understanding this causal relationship correctly is significant since it explains why cancers depend so heavily on glucose but not on other nutrients. More importantly, this realization may lead to fundamentally novel and more effective ways to treat cancer.