March 2, 2024

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New Technology Identifies Drugs to Halt the Spread of Melanoma

New Technology Identifies Drugs to Halt the Spread of Melanoma



New Technology Identifies Drugs to Halt the Spread of Melanoma

Researchers have developed an automated platform for screening thousands of drugs to identify those that can prevent the spread of melanoma.

They successfully tested one such drug on mice, offering hope for effective treatments against metastatic cancer.

New Technology Identifies Drugs to Halt the Spread of Melanoma

Metastatic cancer, especially melanoma, remains a significant health challenge, as each tumor may have a unique microenvironment with varying responses to treatment. Melanoma is an aggressively invasive cancer, and once it spreads, survival rates are low.

A characteristic of the metastatic process is the formation of intrinsic cancer cells, specialized protrusions that degrade the extracellular matrix, allowing cells to enter or invade new environments. Finding drugs targeting these intrinsic protrusions is crucial for effectively preventing cancer spread, but currently, there is a lack of screening capabilities for such drugs.

With the development of “Invasion-Block,” everything could change. “Invasion-Block” is an automated, high-throughput screening platform that enables researchers at the Centenary Institute in Australia to assess the effectiveness of various drugs and compounds in targeting intrinsic cancer cells to prevent melanoma spread.

“Melanoma is a formidable opponent, often rapidly spreading and challenging to treat,” said Shweta Tikoo, the lead author of the study. “The key to finding better treatment methods lies in drug discovery, and that’s where the ‘Invasion-Block’ tool plays a crucial role.”

Researchers combined “Invasion-Block” with an automated image analysis pipeline adapted from astrophysics called Smoothen-Mask and Reveal (S-MARVEL). This combination helped eliminate artifacts and significantly improve the quality of intrinsic protrusion microscopic image datasets.

Subsequently, they screened 3,840 drugs from two FDA-approved compound libraries to detect their ability to inhibit the formation of intrinsic protrusions in melanoma cells. The results revealed that the most effective compounds were kinase inhibitors. Kinase inhibitors can block the action of protein kinases, enzymes that add phosphate groups to proteins in a process known as phosphorylation. Phosphorylation can activate or deactivate proteins, influencing their activity and functional levels, often a necessary step in the growth of certain cancers.

The first author of the research report, Da Jiang Guo, stated, “This suggests that these enzymes may be the key to finding therapeutic approaches to curb melanoma spread.”

Among the identified kinase inhibitors, researchers chose to test the effectiveness of an Ataxia-Telangiectasia Mutated (ATM) inhibitor in the laboratory. Using CRISPR gene editing technology, they knocked out the gene responsible for expressing ATM kinase in melanoma cells, resulting in reduced invasiveness and no spread to the lymph nodes in mice, unlike previous cases.

Tikoo stated, “We believe that ATM could be an effective therapeutic target for treating melanoma spread in patients. The combination of ‘Invasion-Block’ and ‘S-MARVEL’ opens up new avenues for finding drugs that can prevent cancer spread.”

Researchers noted that this study marks a significant step in the fight against melanoma, laying the groundwork for future research and the development of novel therapies.

The study has been published in the Proceedings of the National Academy of Sciences (PNAS).

New Technology Identifies Drugs to Halt the Spread of Melanoma

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