A Korean bio company, Therapeutics NMC, and a joint research team from Yonsei University College of Medicine have developed a new substance that selectively attacks metastatic cancer that does not respond to existing anticancer drugs. The team identified a mechanism that kills cancer cells with resistance to anticancer drugs while having almost no effect on normal cells, suggesting the potential for next-generation anticancer drug development.

Professor Park Ki-cheong of the Department of Surgery at Yonsei University College of Medicine, Professor Lim Jin-hong of the Division of Hepatobiliary and Pancreatic Surgery at Gangnam Severance Hospital, Professor Choi Kyung-hwa of Bundang CHA Hospital, and the joint research team from Therapeutics NMC announced on the 5th that they had developed a new substance, “PPS03,” targeting metastatic cancer cells that exhibit resistance to anticancer drugs and confirmed its effectiveness. The research findings were published in the latest issue of the international journal Biomaterials.

One of the major challenges in cancer treatment is resistance to anticancer drugs. This refers to a phenomenon in which cancer cells that initially respond to treatment adapt to the drugs over time, reducing the therapeutic effect. In particular, cancer cells that have acquired resistance often metastasize to other organs, significantly lowering patient survival rates.

Until now, researchers have used strategies to increase reactive oxygen species to kill cancer cells. Reactive oxygen species are substances generated during cellular metabolism and, when accumulated beyond a certain level, they induce cell death. However, because they are generated in normal cells as well as cancer cells, indiscriminately increasing reactive oxygen species has the limitation of damaging normal tissues.

The research team focused on the fact that metastatic cancer cells have metabolic characteristics different from those of normal cells. In particular, they noted that in metastatic cancer cells, “macropinocytosis,” a process that actively takes up large amounts of surrounding fluid and nutrients, occurs vigorously.

The study found that PPS03 is selectively taken up into metastatic cancer cells through this macropinocytosis process.

In contrast, PPS03 was hardly absorbed by normal cells. Once PPS03 enters cancer cells, it releases iron ions and selenomethionine ions, sharply increasing reactive oxygen species and ultimately inducing cancer cell death. Because normal cells do not absorb PPS03, they can avoid damage from increased reactive oxygen species.

The team verified these effects using metastatic cancer cells obtained from tumor tissues of liver cancer patients whose cancers showed resistance to the existing anticancer drug cisplatin. Experimental results showed that PPS03 exhibited strong anticancer effects even in cancer cells that did not respond to existing anticancer drugs.

This study is significant not only because it developed a new anticancer substance, but also because it proposed a strategy to selectively attack cancer cells by exploiting biological characteristics unique to metastatic cancer cells. It is particularly evaluated as having demonstrated the potential to address both drug resistance and side effects, which are considered the most serious issues in the treatment of metastatic cancer.

Professor Lim explained, “PPS03 not only showed therapeutic effects in metastatic cancer with resistance to existing anticancer drugs, but also has the advantage of reducing side effects by not attacking normal cells.”

Professor Park said, “PPS03, for which metastatic cancer-specific anticancer effects have been confirmed through this study, is currently being prepared for clinical research,” adding, “If commercialization is successful, it is expected to present a new treatment paradigm in the global anticancer drug market.”

Resistance to anticancer drugs and metastasis are cited as leading causes of poor cancer treatment outcomes. The research team aims to verify the safety and therapeutic efficacy of PPS03 through future clinical trials and then apply it to actual patient treatment. Particular attention is focused on whether it can provide a new treatment option for patients with metastatic cancer who have failed existing therapies.

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