Fighting Cancers with a Sea Sponge

In 2016, the Food and Drug Administration (FDA) approved the first drug that improved the survival of patients with liposarcoma—a drug made possible by a sea sponge. This drug, eribulin mesylate (commonly called eribulin or Halaven®), was also approved in 2010 for certain patients with breast cancer. The story of how a sea sponge led to a cancer drug spans three decades of NCI-supported research and collaboration among governments, a pharmaceutical company, and universities.

The medicinal properties of natural products, including plants and marine organisms, have long been a productive source of “lead” molecules for researchers developing cancer drugs. In fact, many cancer drugs are based on natural products, including paclitaxel (Taxol®) from the Pacific yew tree for breast and ovarian cancers and vinblastine (Velban®) and vincristine (Marqibo®) from another plant, the rosy periwinkle, for childhood leukemias and other cancers. In fact, a recent review of drug approvals has shown that 49% of all cancer drugs approved by FDA from around the 1940s to the end of 2014 were derived from natural products.

In 1986, Japanese researchers reported on a group of compounds called halichondrins, isolated from the sea sponge Halichondria okadai, that had promising anticancer activity. Subsequently, a team of NCI intramural and extramural investigators discovered that one of the halichondrins from this sponge and other sponge types from the Pacific blocked cell growth by inhibiting the protein tubulin, confirming its anticancer potential and demonstrating its mechanism of action. NCI worked with institutions in New Zealand to obtain a supply of this halichondrin for testing. Because it was present in such small amounts in the sponges, NCI-funded researchers, led by Yoshito Kishi, Ph.D., of Harvard University, developed a way to generate the halichondrin in the laboratory.

Recognizing halichondrin’s potential against cancer, a pharmaceutical company licensed the compound and made a series of modified versions, or analogs, for testing. Positive results from the tests led to the development of one of the analogs, which became known as eribulin, in collaboration with NCI. NCI supported the preclinical studies and early clinical trials of eribulin, and the company subsequently tested the drug in large phase III clinical trials.

NCI’s extensive work and investment, as well as the interplay of academia, industry, and government, played important roles in developing and bringing eribulin to market over the course of two decades. NCI-funded scientists demonstrated that eribulin was as efficacious as pure halichondrin and could be provided in more sufficient quantities. This persuaded a pharmaceutical company to continue its studies and development of eribulin and ultimately brought an effective therapy to cancer patients who had otherwise exhausted their treatment options.