A recent study conducted by researchers at the Broad Institute of MIT and Harvard University uncovered that a small group of cancer cells is responsible for recurrence.

Considering that most deaths related to cancer are not the result of the first tumor, but recurrence after treatment, this finding could have life-altering results for patients.

This study was published in Nature.

The Study

This investigation studied persister cells, which have been believed to cause cancer recurrence. They are quite rare, accounting for just a fraction of all cancer cells.

These cells survive cancer treatment, and then gain new mutations, continuously allowing them to evade treatment, and grow new tumors.

This team was focused on studying an even smaller group of persister cells called cycling persister cells. Scientists had previously discovered this subgroup, but they were extremely hard to study. Not only were they very rare (5 in every 1,000 persister cells),  they were also hard to track. Cycling persister cells don’t just survive once but can survive even when the cancer is being constantly treated.

Co-senior authors of this trial Joan Brugge and Aviv Regev, as well as lead author Yaara Oren, uncovered a new way to track cycling persister cells. They also utilized single-cell genomics to profile them.

As a result of this study, the team was able to identify the very characteristics of these cells which make them resistant to treatment. They also uncovered which biochemical pathways help them grow.

Tracking Cycling Cells

The research team treated persister cells with common cancer-treatments which are FDA approved. Then, they monitored the cells. They uncovered that the cycling persister cells do indeed act different. Cycling cells each had a unique RNA profile and their variance to normal persister cells was present in both mouse models, human cells from lung tumors, as well as many other types of cancer.

In order to first separate the two types of cells they created a system called Watermelon. This system allowed them to label and track the live cells with a microscope. Each cell was marked with red, and that red became fainter as the cells divided. A green tag also marked different cell lineages.

Some of the characteristics they were able to determine are different for cycling cells include the following.

Cycling cells-

• Had increased antioxidant gene expression programs
• Produced metabolites which were distinct
• Utilized fatty acids to aid their metabolism (most cancer cells utilize glucose)

All of these differences from normal persister cells might explain why they are so resilient. It also may help us to understand how to actually prevent recurrence and mutations which make the cells more resistant to treatment.

Looking Forward

Researchers are hopeful that this research could explain both why past promising investigative cancer therapies have not succeeded, as well what potential therapies could actually work.

This study was a stepping stone. Hopefully it will lead to new therapies for a wide array of cancers which can help to minimize or fully prevent recurrence.

In fact, the researchers in this study have started this inquiry. Finding that fatty acid cells drive cycling persister cells, the team treated lung cancer cells with both standard treatment and a fatty acid oxidation inhibitor. In these cells, the fraction of the cycling persister cells did decrease.

It goes without saying that this study has brought many researchers hope. Most valuably, the knowledge of the characteristics of these cells may be able to support therapies for many different types of cancers, including those that are rare.

You can read more about this study here.