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New drug kills dormant cancer cells

Teresa Tanoos's picture
New drug found that selectively kills dormant cancer cells in tumors by inducing mitochondrial dysfunction

A new study published in the journal Nature Communications reports that a new drug has been discovered that can kill dormant cancer cells in tumors.

The study, led by Professor Stig Linder of the Karolinska Institute in Sweden, found that the drug works by inducing mitochondrial dysfunction, a process that causes the mitochondria to stop working properly.

As a result of this process, dormant cancer cells end up dying because they are no longer getting enough oxygen and nutrients to survive, grow and spread.

Due to insufficient blood vessel growth, solid tumors that are larger than a few millimeters typically lack enough oxygen and nutrients for the cancer cells to divide and grow, which causes the cancer cells to become dormant.

After oxygen and nutrients are fed to these dormant cancer cells, however, they start to divide and tumors begin growing. This progression plays a role in the resistance of solid tumors to radiotherapy and chemotherapy.

But this new study found that in portions of tumors that were not receiving enough oxygen and nutrition, there was also not enough production of mitochondrial energy for the cancer cells to make up for.

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According to the researchers, their findings indicate that when tumor cells are in a nutritionally lacking environment, they become sensitive to disturbances of mitochondrial activity, which results in a “bio-energetic catastrophe".

The researchers also reported that a small molecule known as VLX600 was found to effectively kill off dormant colon cancer cells by inducing mitochondrial dysfunction.

Using a variety of in vivo and in vitro models, the VLX600 molecule was applied to colon cancer cells, which confirmed the induction of mitochondrial dysfunction that caused the cancer cells to die.

While applying VLX600 to colon cancer cell lines in vivo, researchers discovered that it destroyed tumor growth.

In addition, VLX600 gave a boost of power to the drug irinotecan, which has been used to treat colon cancer for some time.

The researchers said that their discovery suggests that cancer cells in nutritionally compromised environments have a reduced “ability to respond to decreased mitochondrial function”; thus, providing a strategy “for targeting the quiescent populations of tumor cells for improved cancer treatment."

The team reports that they’ve developed a drug containing the VLX600 molecule in collaboration with a biotech company located in Sweden. They plan to conduct a clinical study of the drug with American researchers later this year.

SOURCE: Nature Communications, Induction of mitochondrial dysfunction as a strategy for targeting tumour cells in metabolically compromised microenvironments, Stig Linder et al., published February 18, 2014.