New Harvard Anticancer Molecule is a Synthetic Biology Breakthrough

New Harvard Anticancer Molecule is a Synthetic Biology Breakthrough

Cami Rosso 18/06/2019 5

Over three decades ago, Japanese researchers discovered a naturally occurring chemical in certain types of sea sponges with powerful anticancer properties called halichondrin. Sea sponges are invertebrate animals that lack true tissues and organs; they rely on water flowing through the pores of their spongy bodies to provide nutrients and eliminate waste for survival. In nature, halichondrin occurs in extremely small quantities—blocking the ability for scientists to study, test and develop it into a drug to fight cancer—until now. In a remarkable synthetic biology achievement, Harvard University chemists announced today the creation of synthetic halichondrin, a new anticancer drug candidate called E7130.

Synthetic biology is a rapidly emerging field of science that includes both the design and formation of entirely new biological systems or components, and the redesign and production of natural biological systems. Synthetic biology is used not only for scientific research purposes, but also to advance genomics, pharmaceuticals, biotechnology, agriculture, materials science, energy, industrial enzymes, biochemicals, biosensing, flavor, and fragrances. In this case, a synthetic version of a naturally occurring chemical in sea sponges was created.

A study published on June 17, 2019 in Scientific Reports led by Harvard Professor Yoshito Kishi along with collaborators from Eisai, a Japanese pharmaceutical company, reports achieving the total synthesis of halichondrin in quantities that will enable anticancer drug discovery and development. The chemists reported successfully producing synthetic halichondrin with over 99.8 percent purity, under good manufacturing conditions, on an over 10-gram scale—a sufficient quantity for clinical studies.

According to the study, halichondrins have shown powerful antitumor abilities in mice studies that were in vivo, and “excellent in vitro activities towards a variety of human cancer cell types” in various other scientific studies. Yet halichondrins have not been researched in human anticancer research in the past due to the challenges in isolating it in sufficient quantities from sea sponges, or artificially recreating it in a lab. Now this barrier is lifted with the creation of a synthetic halichondrin, E7130.

This achievement was a daunting challenge. According to a report released today in The Harvard Gazette, E7130 is “particularly challenging to replicate because it has 31 chiral centers, asymmetrical points that must each be correctly oriented,” and that there are “roughly 4 billion ways to get it wrong.”

The researchers wrote, “E7130 exhibited potent antiproliferative activities against several cancer cell lines in vitro,” and that it “exerted significant and dose-dependent” antitumor activities with tumor regression in “KPL-4 HER2-positive breast cancer and OSC-19 squamous cell carcinoma of the head and neck.”

E7130 is described by the chemists in the study as “a novel microtubule dynamics inhibitor” that “can also increase intra-tumoral “CD31-positive endothelial cells and reduce α-SMA-positive cancer-associated fibroblasts at pharmacologically relevant compound concentrations.”

The researchers are focused studying E7130 as a potential monotherapy for rare cancers to test the hypothesis that it will be highly effective in fighting cancers where there are many cancer-associated fibroblasts (CAF). The new molecule E7130 is currently in a Japanese Phase I clinical trial. Eisai has a license agreement with Harvard's Office of Technology Development (OTD), and has aspirations to initiate a second clinical trial in the United States in the future.

Copyright © 2019 Cami Rosso All rights reserved.

References

Rosso, Cami. “Synthetic Biology — Life Redesigned.” Medium. March 2, 2017. Retrieved from //medium.com/@camirosso/synthetic-biology-life-redesigned-e96b83fd9648.

Kawano, Satoshi, Ito, Ken, Yahata, Kenzo, Kira, Kazunobu, Abe, Takanori, Akagi, Tsuyoshi, Asano, Makoto, Iso, Kentaro, Sato, Yuki, Matsuura, Fumiyoshi, Ohashi, Isao, Matsumoto, Yasunobu, Isomura, Minetaka, Sasaki, Takeo, Fukuyama, Takashi, Miyashita, Yusuke, Kaburagi, Yosuke, Yokoi, Akira, Asano, Osamu, Owa, Takashi, Kishi, Yoshito. “A landmark in drug discovery based on complex natural product synthesis.” Scientific Reports. June 17, 2019.

Perry, Caroline. "Chemists’ breakthrough in synthesis advances a potent anti-cancer agent." The Harvard Gazette. June 17, 2019.

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  • Dave Smith

    Ground breaking discovery.

  • Andrew Jamieson

    Harvard researchers are the best, they deserve more funds.

  • Michael Houghton

    Yesterday is history, tomorrow is mystery. But today is a gift.

  • Chris Mcguill

    Wow this is awesome.

  • Gabriel Leahy

    Marvelous news

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Cami Rosso

Science Guru

Cami Rosso is an insatiably curious omnidisciplinary writer on science, innovation and leadership.

   

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