Metastasis is the process of cancer spreading through the body. It happens when cells break away from a tumor, traveling around the body to implant themselves in other areas. Unfortunately, this phenomenon renders chemotherapy and immunotherapy pretty ineffective. For decades, the exact mechanisms of how the unwelcome disease travels has been a mystery.

The magic MTDH gene

Thankfully, a research team from Princeton University may have finally cracked the code! The laboratory uncovered the key gene implicated in metastatic breast cancer, named metadherin (MTDH). Further studies in cancer patients showed higher levels of activity of this gene, also linking this to increased treatment resistance.

The scientists realized MTDH’s heavy importance in metastasis and cancer progression, though were able to confirm it had no role in normal healthy bodily functioning. Trials in mice removing the gene yielded not only healthy animals, but also massively decreased rates of metastasis.

Finding the breakthrough drug

This experiment inspired the team to find a drug that can act like this, whilst avoiding invasive gene editing. The paper, published in Nature Cancer, discusses a compound described as a “silver bullet,” which can solely target MTDH, diminishing its activity. Years of protein analysis and drug discovery studies uncovered the most suitable and safe compound to halt the gene in its tracks. Amazingly, the use of this drug in mice resulted in profound anti-cancer effects, the same level as the ones who had the gene removed completely!

Why is this finding so important?

As metastasis is the primary cause of death from the disease, figuring out this problem could save many lives across the globe. Minhong Shen, a member of the laboratory stated: “Our work identified a series of chemical compounds that could significantly enhance the chemotherapy and immunotherapy response rates in metastatic breast cancer mouse models. These compounds have great therapeutic potential.”

The team is now figuring out how to perfect the drug, increasing effectiveness and also decreasing its cost. The team hope clinical trials will take place in human cancer patients in around two to three years.

Source study: Nature Cancer – Small-molecule inhibitors that disrupt the MTDH–SND1 complex suppress breast cancer progression and metastasis