In cancer treatments such as chemotherapy, hundreds of thousands of cancerous cells are killed off. But if even one of these cells has a unique mutation, it can survive the treatment and start to multiply, giving rise to a set of more drug-resistant cells. Researchers at the Salk Institute in California have now gained new insights into what exactly is causing these variations in the cells, suggesting there may in fact be a way of switching off the mechanism and improving treatment effectiveness.

Lead by staff scientist Fernando Lopez-Diaz, the Salk researchers set about identifying the diversification switch, that is, what mechanism was causing the cancers cells to multiply and take on slightly different forms. If this process could be prevented from happening, it may well curtail the cells' ability to develop the resistance to cancer-fighting drugs.

"Cancer isn’t one cell but it’s an ecosystem, a community of cells," says Beverly Emerson, professor at Salk's Regulatory Biology Laboratory. "This study begins the groundwork for potentially finding a way to understand and dial back cell diversity and adaptability during chemotherapy to decrease drug resistance."

In investigating the origins of this diversity, the researchers treated human pre-cancer and metastatic breast cancer cells with paclitaxel, a cancer-fighting drug. The cells that survived started to multiply, though with minor changes in their RNA, a molecule that decodes genes and produces proteins.

The scientists monitored more than 80,000 RNA molecules for each of the new cancer cells. This was a much more thorough examination than other studies, where only hundreds of RNA have been observed to determine the diversification in the molecules. The exhaustive nature of the RNA study shone new light on subtle differences between the generations of the same cancer cells treated with chemotherapy, while also enabling the team to chart how they enhanced diversity through the RNA.

"We found an overwhelming return to diversity after chemotherapy treatment that couldn’t be explained by expected mechanisms," says Lopez-Diaz. "There is something else going on here, a ‘philosopher’s stone’ to cancer cell diversity that we now know to look for."

Additionally, the team found that a large number of the pre-cancer cells subject to chemotherapy survived and multiplied at a higher rate than both normal or cancerous cells. This suggests that the pre-cancer cells would be more resistant to drugs once they developed into a tumor.

"The pre-cancer cells, when exposed to chemotherapy, evolved much faster and create a more drug-resistant state," says Lopez-Diaz. "This and other findings can now be explored into greater detail using the knowledge and perspective we have gained here."

You can hear from Lopez-Diaz in the video below.

The team's research was published in the journal PNAS.

Source: Salk Institute

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