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New drug candidate starves dormant cancer cells

In a study published in Nature Communications, researchers at Uppsala University and Karolinska Institutet present a new drug candidate which selectively kills dormant cells within a cancer tumour through starvation.

These tumour cells, which are found in less oxygenated parts of solid tumours, are resistant to conventional treatments. In solid tumours larger than a few millimetres, there is usually a lack of both oxygen and nutrients due to insufficient blood vessel growth. This in turn results in cancer cells falling into a state of dormancy. This phenomenon therefore contributes to resistance of solid tumours to radio- and chemotherapy. After treatment, such dormant cells will start to divide and tumours will grow.

“In this study we wanted to use the unique environment which exists in tumours to find something that is extra poisonous to these cancer cells”, says Mårten Fryknäs, senior lecturer at the Department of Medical Sciences, Uppsala University, in a press release.

The researchers identified a molecule named VLX600 which in different tests has proven to be effective against colon cancer cells deep inside a tumour.

“VLX600 is a mild inhibitor of mitochondrial respiration, and we have found that dormant cancer cells have a limited possibility to compensate decreased mitochondrial function by increased glycolysis. The dormant cancer cells therefore die of starvation”, says Stig Linder, Professor of experimental oncology at Karolinska Institutet and leader of the study. in a press release.

The research group at Uppsala University was led by Professor Rolf Larsson at the Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.

The VLX600 molecule has been developed in cooperation with Uppsala-based biotech company Vivolux AB, where Stig Linder is also a board member. A clinical study of the substance in collaboration with American researchers is planned to take place this year. The research has been funded by grants from the Swedish Cancer Society, the Cancer Research Foundations of Radiumhemmet, the Swedish Research Council, the Alex and Eva Wallström Foundation and Swedish Foundation for Strategic Research.

Source: Uppsala University