New breakthrough: Treating brain cancer with marine actinomycetes

A new drug specifically for neuroblastoma is exploited from a bacterium found on the seabed at a depth of 1981m . At the University of California Irvine (UCI) Medical Center, a phase 2 trial is underway for the drug, with positive results.

The cancer treatment power of marine actinomycetes

Mr. Paul Jensen, a scientist from the Scripps Institute of Oceanography (University of California San Diego) is paying attention to the layers of sediment that cover the ocean floor. Invertebrates that cling to the surface of the terrain contain countless creatures that cannot be seen with the naked eye, including marine bacteria.

Although small, marine bacteria play a role in recycling nutrients in the ocean and providing food for other organisms. Many marine bacteria also produce chemicals to defend themselves against predators and disease-causing microorganisms.

The research vessel is operated by the Ocean Exploration Foundation (OET), on a voyage to hunt for marine bacteria that cure cancer. (Image source: Ocean Exploration Trust/NautilusLive)

Because of their mechanism of attracting, detecting, and destroying other bacteria, some marine bacteria are also useful to humans. From this bacterium, scientists have created powerful anti-tumor drugs, antibiotics, antivirals and other drugs.

Mr. Paul Jensen discovered many useful molecules in the sea when collecting samples at a depth of 2000m below the sea surface. Because deep-sea bacteria constantly have to adapt to their environment, the compounds they produce are often unique.

More than 60% of active compounds have been found in bacterial species to date. Nearly 75% of that has come from a single class of bacteria: Actinomycete (actinomycetes) . Scientists have discovered countless new drugs derived from actinomycetes that live in the soil.

They also isolated the first actinomycetes with anti-tumor properties and created many drugs used to treat leukemia, lymphoma and several other cancers. However, in the 1980s, when the supply of new compounds was dwindling, pharmaceutical companies began to rush to find new types of actinomycetes.

The journey of medicines from the sea

In 1988, Paul Jensen, then a laboratory technician, joined his partner William Fenical, a chemist from the Scripps Institute, to focus on finding drugs in nature. In June 1989, the Fenical-Jensen duo went to the Bahamas to collect seabed sediment samples from 15 different locations at a depth of 33m.

Back in the lab when growing the samples, the two scientists found 289 separate actinomycetes. Among the bacteria, they discovered a new genus of the bacterium Salinispora that has never been seen on land. They also found the bacterium Salinispora that lives only in salt water. Working with a group of colleagues, Jensen eventually identified two species of Salinispora in the Bahamas samples, both of which produced unique active compounds.

One of them, the bacterium S. tropica, created a molecule that completely changed the two men's careers. When Mr. Fenical tested it with an incurable human colon cancer cell line, the compound produced spectacular results.

Salinispora tropica can be grown in the laboratory. (Image source: Stephanie Stone)

At the US National Cancer Institute (NCI), when testing the new compound with 60 different cancer cells, the results were surprising: The compound that they named Salinosporamide A was effective against several lines of cancer. letters.

In 2001, Dr. Paul Jensen and colleagues sequenced the genome of the bacterium S.tropica and found that nearly 10% of its DNA (the largest percentage known from the species) produced 17 compounds. activity that is largely not revealed through culture.

Today, Dr. Jensen and other team members have created even more tools to track down more molecules. They were able to mine all the molecules in those same samples to find chemical structures that match the assembly instructions in gene clusters.

Since the initial discovery of the Salinosporamide A inhibitor, Scripps Institute scientists have found more than 100 active compounds.

Fenical and Jensen see how the compound Salinosporamide A works against cancer strains. At the Nereus Pharmaceuticals (NP) research center, scientists took the compound Salinosporamide A through standardized steps.

The compound works by targeting the cell's proteasome (a type of trash can that chews up used proteins) and prevents it from working, eventually clogging and killing the cell. . Scientists admit that this is an important way to destroy bone marrow cancer (or myeloma). So NP company has focused on eradicating this disease.

By 2007, they were using Salinosporamide A (also called Marizomib) for a phase 2 clinical trial in patients with multiple myeloma.

Despite success in eradicating multiple myeloma cells, many clinical patients have reported temporary neurological side effects including dizziness and impaired speech.

Over the next few years of research into glioblastoma stem cells, the scientists focused on proteasome inhibition as a promising strategy for targeting the tumors of this disease.

To date, one drug, marizomib, has made progress in a phase 2 clinical trial, and a pharmaceutical company has invested in a follow-up trial.

Neuroblastoma is one of the most dangerous types of tumor. The average survival time of patients with this disease since detection is just 15 months, making it the deadliest brain cancer death. Worse, the disease causes a host of neurological side effects, including paralysis, loss of speech, vision loss, and seizures. If really successful, new drugs from bacteria of the sea will be a bright future for unfortunate patients with this disease.