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May 23, 2019
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Weighing Cells Offers New Potential for Cancer Treatment: Study

WASHINGTON: Many cancer patients are concerned about whether an expensive drug treatment is effective or not.

Now American researchers came up with a testing method: weighing the cancer cell and measuring its growth rate.

A study published in this week’s issue of the journal Genome Biology described the new way to investigate why some cancer cells survive drug treatment while others succumb, which might also lend clue to new drug targets.

“By measuring a cell’s mass and growth rate immediately prior to single-cell RNA-sequencing, we can now use a cell’s ‘fitness’ to classify it as responsive or non-responsive to a drug,” said the study’s senior author Alex K. Shalek, assistant professor of chemistry at Massachusetts Institute of Technology (MIT).

MIT researchers previously invented a technology that could measure the mass of single cells and cell growth rates by repeatedly weighing the cells over short periods of time.

Scott Manalis, a biological engineering professor at MIT and also the study’s senior author, and his colleagues used this approach to test drug responses of tumor cells from patients with multiple myeloma, a type of blood cancer.

After treating the cells with three different drugs, the researchers measured the cells’ growth rates and found they were correlated with the cells’ susceptibility to the treatment, according to the study.

WEIGH, THEN TAKE SNAPSHOTS
In their new study, the researchers added a genomic analysis, offering a snapshot of which genes are being expressed in a single cell at a particular moment.

The researchers weighed cells multiple times within 20 minutes to determine growth rate, and as soon as they reached the end of the channel, they were immediately captured and ruptured to release their RNA for analysis.

Then, they analyzed cancer cells derived from a patient with glioblastoma, an aggressive type of brain cancer.

The researchers treated the cells with an MDM2 inhibitor, a type of drug that can stop tumor formation and is now in clinical trials. In animal studies, this drug has been effective against tumors, but the tumors often grow back later.

They treated the cells, measured their growth rates about 16 hours after the treatment and then sequenced their RNA.

The researchers finally found a population of cells that were not responsive to the drug.

RNA sequencing revealed that in cells that were responsive, genes required for programmed cell death were turned on.

However in cells that did not seem to be vulnerable to the drug, genes linked with a signaling pathway were turned up.

Exploiting these targets could help knock out the defenses that cells use to overcome the original drug treatment, according to the researchers.

The researchers now plan to explore the possibility of targeting some of the genes that were turned up on the non-responding cells, in hopes of developing drugs that could be used together with the original MDM2 inhibitor.