Researchers in the laboratory studying eribulin mesylate
4-minute read
Learn how a Sea Sponge Is Helping to Fight Metastatic Breast Cancer
Halichondria okadai and the eribulin compound
Sitting motionless on the ocean floor gently filtering water for nutrients, the sea sponge Halichondria okadai may seem like an unlikely hero in the fight against metastatic breast cancer. But contained within their porous bodies lies a compound that is uniquely effective at destroying cancer cells: halichondrin B.1 This discovery inspired intensive investigations that, after decades of research, yielded a breakthrough in the form of a refined compound similar to halichondrin B called eribulin mesylate that would go on to be known as HALAVEN.2,3
From the sea to patients
Cancer cells reproduce and grow in an uncontrolled manner due to mutations in the genes.4 This growth process occurs by cell division, called mitosis.4 Microtubules are tiny structures that are essential to mitosis as well as other cellular processes.5 What does any of this have to do with sea sponges? The naturally occurring compound, halichondrin B, and its pharmaceutical counterpart, eribulin mesylate, have distinct structures that bind with the microtubules, interrupting mitosis and ultimately killing the cancerous cells.6 The video below explores the journey of this fascinating compound from the sea to patients.
Let’s geek out with the science here for a moment. Don’t worry if biochemistry isn’t your thing: no lab coat is required.
Anatomy of a cancer killer
You can think of a microtubule as a tiny spring that tightly coils up to form a tube. These tubes have a “minus end” that attaches to the core of the cell and a “plus end” where its growth occurs.5 Eribulin mesylate binds with these growing plus ends, thus inhibiting or disrupting the microtubules from completing their job in mitosis. Not only does this inhibition prevent the cancerous cells from dividing and reproducing, it also causes the cell to trigger its self-destruct mechanism, called apoptosis.7
HALAVEN bonding to microtubules
Apoptosis is a natural process that many cells undergo as a normal part of the body’s growth and development.8 In this case, the cancerous cells detect that something is awry, and they are hardwired to undergo apoptosis rather than divide improperly. Eribulin mesylate essentially tricks the cancerous cells into killing themselves.6 And that’s not all.
Eribulin mesylate is also thought to work in another surprising way: by helping the tumor breathe.9,10 While that may sound counterintuitive, the science behind it is fascinating.
In simple terms, tumors are clusters of cancerous cells growing rapidly out of control. They aren’t just getting larger: they’re a big, jumbled mess lacking the sophisticated infrastructure that our bodies have in place for healthy organs.10 This means that cancer cells are not getting enough oxygen, a condition a known as hypoxia.11 Cancer cells not getting enough oxygen—that should be a good thing, right? Not so fast. Tenacious little things that they are, cancer cells desperate for oxygen change their behavior in order to acquire it, including spreading to other regions.10 And that can be very problematic.
Laboratory research suggests that eribulin mesylate changes the structure of blood vessels, increasing blood flow to the parts of the tumor that lack oxygen.9 Further evidence indicates that eribulin mesylate may change the way the cancer cells move and spread throughout the body.10
Learn more about how HALAVEN works
Conclusion
Inspired by a naturally occurring compound found in sea sponges, HALAVEN is the first agent in the halichondrin class. Its dual action of destroying cancer cells and changing the internal environment around the tumor makes it a potent compound in the fight against cancer.
- Hirata Y, Uemura D. Halichondrins—antitumor polyether macrolides from a marine sponge. Pure Appl. Chem. 1986;58(5):701-710.
- Towle, MJ, Salvato KA, Budrow J, et al. In vitro and in vivo anticancer activities of synthetic macrocyclic ketone analogues of halichondrin B1. Cancer Res. 2001;61(3):1013-1021.
- US FDA approves Eisai’s HALAVEN™ (eribulin mesylate) injection for treatment of metastatic breast cancer. Press Release. Eisai Global. November 16, 2010. Accessed June 2, 2021. https://www.eisai.com/news/news201064.html
- Bavle RM. Mitosis at a glance. J Oral Maxillofac Pathol. 2014;18(suppl 1):S2–S5.
- Brenner L. What are the main function of microtubules in the cell? Sciencing.com. Updated August 31, 2018. Accessed June 2, 2021. https://sciencing.com/main-function-microtubules-cell-8552402.html
- Jordan MA, Kamath K, Manna T, et al. The primary antimitotic mechanism of action of the synthetic halichondrin E7389 is suppression of microtubule growth. Mol Cancer Ther. 2005;4(7):1086-1095.
- Smith JA, Wilson L, Azarenko O, et al. Eribulin binds at microtubule ends to a single site on tubulin to suppress dynamic instability. Biochemistry. 2010;49(6):1331-1337.
- Austin CP. Apoptosis. National Institutes of Health. National Human Genome Research Institute. Accessed June 2, 2021. https://www.genome.gov/genetics-glossary/apoptosis
- Funahashi Y, Okamoto K, Adachi Y, et al. Eribulin mesylate reduces tumor microenvironment abnormality by vascular remodeling in preclinical human breast cancer models. Cancer Sci. 2014;105(10):1334-1342.
- Dybdal-Hargreaves NF, Risinger AL, Mooberry SL. Eribulin mesylate: mechanism of action of a unique microtubule-targeting agent. Clin Cancer Res. 2015;21(11):2445-2452.
- Merriam-Webster. Hypoxia. Accessed June 2, 2021. https://www.merriam-webster.com/dictionary/hypoxia
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Who is HALAVEN (eribulin mesylate) Injection for?
HALAVEN is a prescription medicine used to treat adults with breast cancer that has spread to other parts of the body, and who have already received other types of anticancer medicines after the cancer has spread.
What safety information do I need to know about HALAVEN?
HALAVEN can cause serious side effects, including
- Low white blood cell count (neutropenia). This can lead to serious infections that could lead to death. Your health care provider will check your blood cell counts. Call your health care provider right away if you develop fever (temperature above 100.5°F), chills, cough, or burning or pain when you urinate, as any of these can be symptoms of infection
- Numbness, tingling, or pain in your hands or feet (peripheral neuropathy). Peripheral neuropathy is common with HALAVEN and sometimes can be severe. Tell your health care provider if you have new or worsening symptoms of peripheral neuropathy
- Your health care provider may delay or decrease your dose or stop treatment with HALAVEN if you have side effects
Before you receive HALAVEN, tell your health care provider about all of your medical conditions, including if you
- have liver or kidney problems
- have heart problems, including a problem called congenital long QT syndrome
- have low potassium or low magnesium in your blood
- are pregnant or plan to become pregnant. HALAVEN can harm your unborn baby. Tell your health care provider right away if you become pregnant or think you are pregnant during treatment with HALAVEN. Females who are able to become pregnant should use an effective form of birth control during treatment with HALAVEN and for at least 2 weeks after the final dose of HALAVEN and males should use an effective form of birth control when having sex with female partners who are able to become pregnant during treatment with HALAVEN and for 3½ months (14 weeks) after the final dose of HALAVEN
- are breastfeeding or plan to breastfeed. It is not known if HALAVEN passes into your breast milk. Do not breastfeed during treatment with HALAVEN and for 2 weeks after the final dose of HALAVEN
Tell your health care provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
What are the possible side effects of HALAVEN?
HALAVEN can cause changes in your heartbeat (called QT prolongation). This can cause irregular heartbeats. Your health care provider may do heart monitoring (electrocardiogram or ECG) or blood tests during your treatment with HALAVEN to check for heart problems.
The most common side effects of HALAVEN in adults with breast cancer include low white blood cell count (neutropenia), low red blood cell count (anemia), weakness or tiredness, hair loss (alopecia), nausea, and constipation.
Your health care provider will do blood tests before and during treatment while you are taking HALAVEN.
For more information about HALAVEN, please see full Prescribing Information.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.