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Friday, May 17, 2024

Have scientists finally found the universal cure for cancer?

In what they have called an "unprecedented achievement," researchers have managed to synthesize a powerful anticancer compound. Scientists have been trying to achieve this feat for more than 3 decades.

News Desk |

Yoshito Kishi, who is the Morris Loeb Professor of Chemistry in the Department of Chemistry and Chemical Biology at Harvard University in Cambridge, MA, is the lead researcher of this scientific endeavor, and the compound in question is called “halichondrin.”

Halichondrin occurs naturally in the sea sponge Halichondria okadai. A team of Japanese-based researchers discovered it in its natural state 33 years ago. However, in sea sponges, scientists have only found halichondrin in minuscule quantities.

The research team “have completed a remarkable total synthesis, enabling us to initiate a clinical trial of E7130.

To study its pharmacological properties and biological behavior, as well as to test its anticancer effects, researchers needed larger quantities. So, since then, they have been trying to synthesize the E7130 halichondrin molecule. However, the structure of this molecule made it particularly difficult to recreate.

Also, trying to synthesize small amounts of it impacted the formation of microtubules, explain Prof. Kishi and his colleagues, which are indispensable for the division of a cell.

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The importance of halichondrin

When researchers first discovered it, they “realized the halichondrins looked exceedingly potent,” explains study co-author Takashi Owa. “Due to the very unique structure of the natural product, many people were interested in the mode of action, and the investigators wanted to do a clinical study, but a lack of drug supply prevented them from doing it. So, 30 years have passed,” he goes on.

To study its pharmacological properties and biological behavior, as well as to test its anticancer effects, researchers needed larger quantities.

Owa is also the Chief Medicine Creation Officer and Chief Discovery Officer at Eisai’s oncology business group. Eisai is a Japanese pharmaceutical company that worked with Harvard scientists for 3 years in order to achieve the synthesis.

Now, Prof. Kishi and colleagues have surmounted these obstacles and “achieved a total synthesis of […] E7130” on a scale larger than 10 grams with more than 99.8% purity. They detail their findings in the journal Scientific Reports.

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‘Unprecedented achievement of synthesis’

In 1992, Prof. Kishi and team were the first researchers to achieve the total synthesis of a halichondrin molecule called halichondrin B. In 2010, a simplified version of the molecule — called eribulin — became available to treat metastatic breast cancer and liposarcoma.

However, “[i]n 1992, it was unthinkable to synthesize a gram-quantity of a halichondrin,” says Prof. Kishi. But now, “[o]rganic synthesis has advanced to that level, even with molecular complexity that was untouchable several years ago.”

When researchers first discovered it, they “realized the halichondrins looked exceedingly potent,” explains study co-author Takashi Owa.

“We are very delighted to see our basic chemistry discoveries have now made it possible to synthesize this compound at large scale,” adds Prof. Kishi. “It’s a really unprecedented achievement of total synthesis, a special one […] No one has been able to produce halichondrins on a 10-gram scale — one milligram, that’s it”, says Takashi Owa.

The research team “have completed a remarkable total synthesis, enabling us to initiate a clinical trial of E7130,” Owa continues.

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In their paper, the scientists also describe new insights into the mechanism of action of E7130. In the past, researchers showed that halichondrins can inhibit microtubules, and thereby exert anticancer properties. But E7130 also has unique effects; it changes the tumor environment, which may improve how well other cancer drugs work.