LF3 May Emerge as Potent Weapon Against Mesothelioma Stem Cells

Your fight with mesothelioma is difficult for several reasons. One reason is that the asbestos cancer always seems to bounce back with a vengeance after it has been successfully knocked down.

The explanation for this is that one or more of the tiny number of mesothelioma cells that invariably manage to survive treatment contain stem cells. They allow mesothelioma tumors to regenerate and respread.

Researchers from the Max Delbrück Center for Molecular Medicine in Germany think they have developed a drug that will prevent stem cells from supporting cancer cell regeneration.

The drug is a compound they’re labeling LF3. In testing on lab mice, LF3 was found to interrupt tumor cell life cycles.

This interruption resulted in the cells becoming incapable of replicating themselves. It also resulted in tumors being significantly less able to migrate to other parts of the body.

Better still, LF3 has no apparent harmful impact on healthy cells. The icing on the cake is that LF3 appears to induce conversion of the surviving cancer cells into benign tissue.

Mesothelioma Stem Cells are Bad News

Here is what you need to know about cancer stem cells. In brief, they’re bad news. This is why. Stem cells give birth to other cells. If the stem cells are cancer stem cells, the cells they birth will also be cancerous.

All of the cells making up a tumor come from one starter stem cell. A few of that parent cell’s children and grandchildren will also contain stem cells.

Each of those offspring so endowed will also be able to create tumors. But none of the other offspring cancer cells will be able to do that.

So knocking out stem cells along with the cancer cells is foundationally important when it comes to treating mesothelioma.

An approach taken by mesothelioma researchers to achieve victory involves looking for ways of disrupting the signaling pathways stem cells use.

The signals sent out by stem cells provide instructions to their offspring on how to be successful cancer cells. The offspring cells are left clueless if the signals are disrupted. And clueless offspring cells don’t flourish.

A focus of the research effort to disrupt signaling has been the Wnt signaling pathway. In healthy cells, the Wnt pathway is vital for ensuring that cells and the tissues they form are intact and functioning well.

But when you have mesothelioma – or any type of cancer – the Wnt signaling pathway becomes a slave to the tumor. The pathway is forced to send out signals telling all the offspring cells to run wild.

LF3 Is Beta-Catenin That Binds to TCF4

Of keen interest to the Max Delbrück researchers was a specific piece of the Wnt pathway — the beta-catenin component.

Beta-catenin binds to a protein called TCF4. This coming together provides cancer stem cells the juice they need to operate and send out their destructive instructions, the researchers explained.

The researchers hypothesized that they might be able to develop a drug to disrupt the binding of beta-catenin to TCF4. No binding would mean a disruption of stem cell communication to offspring.

The quest for such a drug began by taking TCF4 molecules and adding to them one at a time a wide assortment of beta-catenin compounds.

The researchers said they were looking for a pairing that resulted in TCF4 and beta-catenin binding at the slowest possible rate. They found it in LF3.

When tested in the mice, it effectively interrupted the cancer cells’ cycling. “We observed a strong reduction of tumor growth,” the researchers reported in the journal Cancer Research.

“What remained of the tumors seemed to be devoid of cancer stem cells,” they continued. “At the same time, no signaling systems other than Wnt were disturbed.”

The researchers concluded that LF3 shows considerable promise as a therapeutic. However, much more comprehensive research into its efficacy and safety must still be conducted.