December 6, 2022

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Starve cancer cells by blocking the uptake of amino acids by cancer cells

Starve cancer cells by blocking the uptake of amino acids by cancer cells

 

Starve cancer cells by blocking the uptake of amino acids by cancer cells. Cancer cells are addicted to this amino acid, blocking its uptake, starving the cancer cells to death.

Starve cancer cells by blocking the uptake of amino acids by cancer cells


A key sign of cancer is the alteration of cancer cell metabolism, which is crucial for the development and development of cancer and treatment resistance. For many cancer cells, they need to take in large amounts of glutamine to provide energy for their rapid growth and division.

The intake of glutamine by cancer cells is mediated by the glutamine transporter SLC1A5. In fact, the expression of SLC1A5 is increased in many cancers, and this increase in expression is also associated with poor survival.

The dependence of cancer cells on glutamine is also called “glutamine addiction.” Blocking the uptake of glutamine will cause cancer cells to stagnate or even die. Therefore, blocking the uptake of glutamine has become one of the treatments for cancer. A promising strategy.

Recently, researchers from the Sanford-Burnham-Pribes Institute of Medical Discovery in the United States published a research paper titled: Identification and Characterization of IMD-0354 as a Glutamine Carrier Protein Inhibitor in Melanoma in the journal Molecular Cancer Therapeutics.

The study identified a small-molecule drug candidate named IMD-0354, which inhibits cancer cells’ uptake of glutamine by targeting the glutamine transporter SLC1A5, blocking cancer cells’ important energy source, thereby slowing cancer Cell growth.

Since glutamine is an important energy source for many different types of cancer cells, the drug is expected to provide a new method for the treatment of many types of cancer.

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The research focuses on melanoma. In the past decade, humans have made great progress in the treatment of melanoma. In particular, cancer immunotherapy represented by immune checkpoint inhibitors has been successfully applied to the treatment of melanoma.

However, cancer immunotherapy is ineffective for most cancer patients, and as the treatment progresses, many cancer patients develop resistance, which has become a major obstacle to the successful treatment of melanoma.

 


Starve cancer cells

Scientists now know that fast-growing tumors can reprogram their metabolism to produce extra energy to survive and grow. Normally, cancer cells use the SLC1A5 protein to transport the amino acid glutamine to cancer cells for energy metabolism.

Based on this discovery, many cancer researchers are committed to finding drugs that can block SLC1A5 and reduce glutamine levels, hoping to starve cancer cells by this method.

 

 

1 in 7000

Based on the above ideas, the research team screened 7,000 small molecule compounds that can interfere with the function of SLC1A5. The research team first screened 20 promising compounds, and then selected one of them, IMD-0354, based on their ability to inhibit SLC1A5 from reaching the cell membrane.

Cell experiments confirmed that IMD-0354 is an effective glutamine absorption inhibitor, which can continuously reduce the intracellular glutamine level.

Then the research team conducted a series of verifications on the anti-cancer effect of IMD-0354. Both in vitro cell experiments and mouse model experiments showed that IMD-0354 can significantly inhibit the growth of melanoma.

The research team further discovered that while inhibiting glutamine uptake, IMD-0354 can also attenuate mTOR signal transduction, inhibit the growth of melanoma cells, induce cell cycle arrest, and enhance autophagy and apoptosis.

In addition, the research team also found that IMD-0354 combined with glutaminase 1 (GLS1) inhibitors or lactate dehydrogenase A (LDHA) inhibitors can enhance the death of melanoma cells.

 


Huge application prospects

Many targeted drugs for the treatment of melanoma often develop resistance after a few months of use, leading to reduced efficacy. Although immunotherapy has broad prospects, not all patients have multiple uses, and drug resistance will also appear.

In this study, the research team confirmed that targeting SLC1A5 can block the uptake of glutamine by cancer cells and effectively slow down the growth of cancer cells. Since many types of cancer rely on glutamine for survival, IMD-0354 is expected to be used Treat many different types of cancer.

It is reported that the research team will focus on improving IMD-0354, improving its biophysical properties, and accelerating the preclinical evaluation of the candidate drug.

 

 

 

 

(source:internet, reference only)


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