Mesothelioma Takes a Beating from Promising New Drug

Scientists associated with the Polaris Group report good news about the company’s experimental drug to treat mesothelioma — it does a fine job of screwing up the internal operations of mesothelioma cells.

The drug is ADI-PEG 20. It appears to trigger destructive changes in the genetic expression of cells that suffer from a shortage of a certain metabolic protein.

It just so happens that one of the cell types affected by this particular shortage is — you guessed it — mesothelioma.

The scientists conducting the work with ADI-PEG 20 come from a number of research centers around the world.

They’ve been finding that just about any cancer cell deficient in the enzyme argininosuccinate synthetase is vulnerable to ADI-PEG 20.

Argininosuccinate synthetase — or ASS1, for short — is used by mesothelioma cells to help process arginine.

Arginine is an amino acid needed by cells to grow and work as designed.

Mesothelioma Cells Steal What They Need

The problem for mesothelioma cells right off the bat is that they don’t have enough ASS1 of their own to process the required levels of arginine.

To get what they lack, mesothelioma cells resort to theft of arginine. They steal it from the circulatory system.

ADI-PEG 20 breaks up this little theft racket by reducing the amount of arginine in the circulatory system. With less arginine available to them, the mesothelioma cells have difficulty growing.

Arginine is one of the 20 amino acids that are essential for protein synthesis and survival of cells.

Consequently, “it is believed that these cancer cells become dependent upon the external supply of arginine to survive and grow,” according to Polaris.

“ADI-PEG 20 is designed to systematically deplete the external supply of arginine, which causes these arginine-dependent cancer cells to die while leaving the normal cells unharmed.”

Multiple Teams Doing Mesothelioma Research

One of Polaris’ research teams observed that ASS1 deficiency causes mesothelioma to behave aggressively. In fact, the greater the deficiency, the greater the aggressiveness.

The team — from the University of Miami — noted that ADI-PEG 20 treatment not only slows tumor growth, it also sets up ASS1-deficient cells to die off.

As a bonus, they found that ADI-PEG 20 treatment may increase the effectiveness of mesothelioma chemotherapy.

Meanwhile, researchers from Barts Cancer Institute in Britain — another Polaris team — linked ASS1 loss to increased cell invasiveness and migration, which occur just before mesothelioma rears its ugly head.

The Barts team also determined that mesothelioma patients with significant ASS1 deficiency have a survival of about six months after diagnosis.

They arrived at that prognosis statistic by examining the medical records of 41 mesothelioma patients.

Like the University of Miami team, the Barts team found that ADI-PEG 20 treatment helped make mesothelioma chemotherapy more effective.

ADI-PEG 20 is right now undergoing a Phase 3 clinical trial. Unfortunately, this trial is not geared around mesothelioma patients – it’s evaluating the drug in patients with hepatocellular carcinoma.

However, Polaris announced that it does plan to conduct clinical trials of ADI-PEG 20 with mesothelioma patients.

Polaris is a privately held multinational biopharmaceutical company that specializes in the research and development of protein drugs to treat cancer and other debilitating diseases.

In addition to ADI-PEG 20, Polaris is researching and developing other biotherapeutic agents.

It also is advancing a small molecule drug program aimed at designing novel compounds to inhibit the biological function of cancer-related protein targets.