Discovery of the "Achilles' Heel" of cancer cells

　　Helps develop new therapies that limit the development of solid tumors

　　Science and Technology Daily, Beijing, August 29 (intern reporter Zhang Jiaxin) Researchers from the University of British Columbia School of Medicine and the Cancer Institute of British Columbia discovered the weakness of a key enzyme called carbonic anhydrase IX (CAIX). When oxygen levels are low, solid tumor cells rely on this enzyme to adapt to the environment and survive.

The results of this study, published on the 27th in the journal "Science Advances", will help scientists develop new treatment strategies that limit the development of solid tumors.

　　Clinically, tumors are divided into solid tumors and non-solid tumors.

Solid tumors rely on blood supply to transport oxygen and nutrients to help them grow.

As the tumor develops, blood vessels cannot provide oxygen and nutrients to every part of the tumor, which leads to the production of hypoxic zones.

Over time, the hypoxic environment will cause the accumulation of acid in tumor cells.

　　In order to overcome this pressure, the cell neutralizes the acidic conditions in the environment by releasing enzymes (one of which is CAIX). In the end, it not only survives, but also becomes a more aggressive type that can spread to other organs. Tumor.

　　"Cancer cells rely on CAIX for survival, which ultimately makes CAIX their'Achilles heel'. By inhibiting the activity of CAIX, we can effectively prevent the growth of cancer cells." The senior author of the study and the University of British Columbia School of Medicine Dr. Shukat De Haar, a professor in the Department of Biochemistry and Molecular Biology, explained.

　　Previously, De Haar's research team discovered a unique compound called SLC-0111, which is a powerful inhibitor of CAIX and is currently in phase I clinical trials.

Although preclinical models of breast cancer, pancreatic cancer, and brain cancer have demonstrated the effectiveness of this compound in inhibiting tumor growth and spread, other cellular properties reduce its effectiveness.

　　In this study, the research team began to use a powerful tool called "full-gene combination into lethal screening" to examine the characteristics of these tumor cells and find other weaknesses in CAIX.

The tool is based on the genetics of cancer cells and can systematically delete one gene at a time to determine whether it can kill cancer cells by eliminating CAIX and another specific gene.

　　De Haar said that the test results unexpectedly found that CAIX can prevent cancer cells from dying due to iron droop (also known as "iron death", a form of cell death).

This form of cell death occurs when iron accumulates and weakens the tumor’s metabolism and cell membranes.

CAIX enzyme inhibitors, including SLC-0111, when combined with compounds known to cause iron prolapse, can cause a large number of tumor cells to die and inhibit tumor growth.

　　It is understood that scientists are conducting a large-scale study in order to determine the drugs that can cause cancer cell iron to sag.

And this new research is an important step forward in this exploration.

　　Editor-in-chief

　　Cancer is an important killer of human health in modern society. Scientists in the field of biomedicine have been tirelessly looking for better ways to treat it.

In recent years, many advances in the treatment of cancer stem from breakthroughs in the understanding of the mechanism of cancer.

For example, the Nobel Prize in Physiology or Medicine in 2018 was awarded to scientists who have made outstanding contributions in cancer immunotherapy.

Theoretically speaking, if we can understand more precisely what is contributing to the occurrence and development of cancer from the cellular or molecular level, we can be more precise and targeted, and achieve a more effective result with half the effort.

From this perspective, the above-mentioned research provides new clues for humans to deal with cancer.