Chemotherapy drug


 27 April 2014

Many cancer patients who undergo chemotherapy stop responding to treatment as a result of their cancer cells developing resistance to drugs. But researchers from the University of Manchester in the UK say they have discovered a way to target these drug-resistant cells, making them more open to therapy.

The research team, led by Dr. Andrew Gilmore, recently published their findings in the journal Cell Reports.

To reach their discovery, the researchers first explored the mechanisms behind mitosis – a process in which cells replicate and divide. They explain that any interference in this process can lead to apoptosis, or “controlled cell death.”

“Failure of cells to complete mitosis correctly can be the start of cancer,” explains Dr. Gilmore. “We wanted to understand how this failure – delay of cell division – activates apoptosis, and why some cancer cells may be able to avoid being killed.”

The team investigated colon cancer cells, some of which were sensitive to Paclitaxel – a drug often used to treat colon and breast cancers – and some of which were resistant. Such medication is used to kill cancer cells by targeting them as they divide. But Dr. Gilmore says there is a lack of understanding as to how these cells become resistant to cancer drugs.

Drug-resistant cells ‘escape Bid activation to avoid death’

Scientists say they have found a way to target drug-resistant cancer cells, which could potentially increase patients’ response to chemotherapy.

From their investigation, the team discovered a key protein that regulates apoptosis, called Bid. This protein is selectively activated by phosphorylation just as cells enter the final stage of mitosis.

The researchers found that drug-resistant cancer cells still triggered the Bid protein, but they were able to escape mitosis before Bid was able to activate apoptosis, meaning the cancer cells were able to avoid being killed.

However, the team discovered that by treating these cancer cells with a drug called ABT-737 – a new class of compounds that target apoptosis regulators – they were able to make them sensitive to Paclitaxel.

Commenting on the study results, Dr. Gilmore told Medical News Today:

“The findings would suggest that all cells, including Paclitaxel-resistant cancer cells, become hypersensitive to apoptosis during mitosis.

It might therefore be possible to sensitize those cells to anti-mitotic drugs using combination therapy with compounds like ABT-737. A number of drugs are in stages of development and trials that target apoptotic regulators like Bid, so this is a possibility in the future.”

He added that the team now plans to study an array of different tumor types, including drug-resistant breast cancer cells, to further determine whether targeting apoptosis may increase response to anti-mitotic drugs.

However, Dr. Gilmore told us that this approach is a long way off widespread use in cancer treatment.

“But,” he added, “it may be possible in the future to increase sensitivity to current chemotherapies by targeting the regulators of apoptosis. Drugs that target these, such as Navitoclax (ABT-263), are looking promising in trials.”

Earlier this year, Medical News Today reported on a study suggesting that giving cancer patients high doses of vitamin D intravenously alongside chemotherapy may boost treatment response.


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