Automation Has Identified Cancer Cell Metabolism Inhibitors

Cell division—the process of dividing one cell into two identical cells with the same genetic material—is a regular occurrence within the human body. Cell division is the primary mechanism by which the body grows and repairs damage. However, in cancerous cells, cell division can spiral out of control. 

Unlike typical cells, cancer cells continue to divide without slowing or stopping. Over time, the excess cells can form the solid masses we know as tumors or proliferate within the blood and overwhelm it with excess, abnormal cells. Thus, much of cancer research is focused on stopping this abnormal cell division before it causes problems within the body.

Scientific Analysis of Cancer Cells

Like other cells, cancer cells require energy in the form of glucose to grow and divide. However, unlike healthy cells—which need energy to carry out normal body processes—cancer cells simply spread and consume energy. While researchers have long been aware that preventing cancer cells from getting the glucose they need also controls their growth and spread, it is difficult to do so without also depriving healthy cells of vital energy. Thus, treatments aimed at limiting glucose to slow cancer growth and make tumors easier to treat have also traditionally harmed healthy cells.

In the past, scientists methodically tested molecules one by one to determine if any effectively slowed cancer cell uptake of glucose but protected healthy cells. This process identified a few potential candidates but was excruciatingly slow. Now, researchers at UCLA have developed an automated robotic testing technique capable of testing more molecules at one time.

A New Method

Modern lab equipment holds the ability to test potential therapeutic molecules against various biological targets, using plates with as many as 384 wells at a time. These machines allow automated testing of hundreds of molecules at a time through a process called molecular screening. The UCLA Molecular Screening Shared Resource facility utilized this sort of equipment to develop a glucose analog designed to mimic the glucose found in the human body. 

In the study, researchers placed lung cancer cells into each of the hundreds of wells of multiple plates, along with individual molecular compounds that were allowed to act upon the cancer cells. Then, the specialized glucose analog was added to the cells and allowed to metabolize. Finally, researchers treated the cells with a bioluminescence enzyme, which produces light when it contacts metabolized glucose. By tracking this light, researchers were able to record how much glucose the cancer cells in each well were able to metabolize.

Future Implications

The automated process developed by the UCLA team will drastically speed testing for therapeutic molecules that inhibit cancer cell metabolism. Although the process has only been used on non-small cell lung cancers to date, researchers hope to utilize the process on other types of cancer cells in the future. 

This study has enabled researchers to isolate molecular compounds that show potential for inhibiting cancer cells’ ability to metabolize glucose and do so more quickly. In the future, molecules screened for this purpose could undergo further study to determine their effects on healthy cells. Those that target cancer cells exclusively could eventually be used to formulate treatments and therapies for cancer. 

Sources: 

http://newsroom.ucla.edu/releases/automated-method-puts-cancer-metabolism-to-the-test 

https://www.nature.com/articles/s41467-019-13334-8 

https://www.cancer.gov/about-cancer/understanding/what-is-cancer 

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