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Apoptosis Induction as a Treatment for Malignant Mesothelioma

Malignant mesothelioma is a devastatingly aggressive form of cancer commonly associated with asbestos exposure over a long period of time. This form of cancer often afflicts people whose careers brought them into contact with asbestos fibers on a daily basis—individuals working in home construction, automobile or vinyl manufacturing, and HVAC. It is a cancer type that can grow and spread rapidly unless diagnosed very early on, and prognosis is often grim.

Mesothelioma often remains in a dormant state, remaining symptomless for several years—sometimes as long as 30 to 40 years—after exposure to asbestos. Thus, the early diagnosis that is so crucial for treatment to be effective is often a challenge. Recent research findings suggest that therapies involving a process called apoptosis induction may hold promise in treatment of this disease.

What is apoptosis?

Apoptosis is a pre-programmed means that causes the death of a living cell within an organism. In other words, it is a form of “cellular suicide,” or a ticking time bomb aimed directly at a specific cell or cell type. Although the process may sound somewhat grim, it is well-documented that apoptosis serves a positive purpose at various stages of human development—for example, in utero when humans have extra tissue connecting their fingers and toes in a web-like formation, apoptosis is responsible for “dissolving” the web material and leaving separate and distinctive digits prior to birth.

Similarly, when development of the central nervous system begins, mass quantities of brain cells are formed—far more than are necessary or even beneficial—and apoptosis is responsible for eliminating the unnecessary cells so that brain development can continue normally.

What causes apoptosis?

In nature, apoptosis tends to be triggered by certain hormonal processes—a timing mechanism of sorts. For example, apoptosis plays a prominent role in first menses. However, apoptosis can at times be pathological—for example, stress can cause apoptosis to occur, and more apoptosis is seen in individuals with certain viruses or neurological dysfunction, such as people with AIDS or Parkinson’s disease. Conversely, people with cancer—such as malignant mesothelioma—show lower than normal rates of apoptosis.

Apoptosis Induction: A Closer Look

If people with malignant mesothelioma tend to have less apoptosis than healthy people, could purposefully inducing apoptosis have a therapeutic effect on those individuals? Several researchers have been wondering just that. Let’s briefly explore their findings:

Disulfiram

Initially intended as a treatment for alcoholism, disulfiram (brand name Antabuse) is a drug that is currently being explored by an international team of researchers as an alternative treatment for malignant mesothelioma. The researchers found that malignant mesothelioma cells, when exposed to disulfiram, the mesothelioma cells became apoptotic and died off. These findings suggest that disulfiram may be a viable treatment option for people with certain types of mesothelioma.

Lovastatin

As the name suggests, lovastatin is a statin drug, typically used to treat high blood cholesterol. However, U.S. researchers at the University of Minnesota also found that lovastatin has another interesting side effect when administered to human malignant mesothelioma cells: it causes them to undergo apoptosis, thus potentially decreasing the growth and spread of mesothelioma tumors. These findings indicate that lovastatin—a well-studied and well-tolerated drug—could be paired with other treatment methodologies to “enhance” their cancer-fighting powers.

Gene Therapy: Antisense and Antisurvivin

In today’s world, with the sciences of genetics and genomics constantly underscoring new discoveries in the fight against cancer, gene therapy is becoming a more and more viable option for the future with regard to malignant mesothelioma treatment. Recent findings by researchers from the United States and Switzerland indicate that gene therapies utilizing antisense and antisurvivin treatments. These treatments induce apoptosis in cancer cells at the most basic level, causing the breakdown of proteins within the cancer cells, thus rendering them inactive. Researchers hope that these forms of gene therapy could work well in eradicating tumors when combined with other means of treatment using a “one-two punch” approach to treatment.

What Does this Mean for the Future of Mesothelioma Treatment?

Researchers hope that finding ways to selectively induce apoptosis of cancerous cells—by gene therapy or by drug therapy—will lead to longer, better lives for those diagnosed with malignant mesothelioma and other types of cancer. If apoptosis induction proves to be successful, it could be the wave of the future for mesothelioma treatment: a treatment that is more targeted than traditional chemotherapy or radiation, with lower incidences of side effects, as well.

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