New drug candidate starves dormant cancer cells

In a study published in Nature Communications, researchers at Karolinska Institutet and Uppsala University in Sweden 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 falling into a state of dormancy. After treatment, such dormant cells will start to divide and tumours will grow. This phenomenon therefore contributes to resistance of solid tumour to radio- and chemotherapy.

In their newly published study, the researchers show that cancer cells located in tumour regions that are poorly oxygenated and lack nutrition are unable to compensate for deficient mitochondrial energy production.

"We have identified a small molecule that we call VLX600, which in various in vitro and in vivo models has proven effective against dormant colon cancer cells that are otherwise very difficult to treat. 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 by starvation" says Stig Linder, the professor of experimental oncology leading the study.

More information: "Induction of mitochondrial dysfunction as a strategy for targeting tumour cells in metabolically compromised microenvironments", Xiaonan Zhang, Mårten Fryknäs, Emma Hernlund,Walid Fayad, Angelo De Milito, Maria Hägg Olofsson,Vladimir Gogvadze, Long Dang, Sven Påhlman, Leoni A. Kunz Schughart, Linda Rickardson, Padraig D'Arcy, Joachim Gullbo, Peter Nygren, Rolf Larsson2 & Stig Linder, Nature Communications, online 18 February 2014, DOI: 10.1038/ncomms4295

add to favorites email to friend print save as pdf

Related Stories

Acidic tumour pH inhibits drug effect

Feb 11, 2014

Low pH in tumours counteracts the desired effect of the drug chloroquine, according to a new study from Karolinska Institutet in Sweden. The results, which are published in the journal Autophagy, might explain ...

Promising results for Swedish cancer drug candidate

Dec 06, 2013

A new study conducted by scientists from the Dana-Farber Cancer Institute at Harvard Medical School and Karolinska Institutet in Sweden presents very promising results for the treatment of the cancer form multiple myeloma. ...

Breaking down cancer's defense mechanisms

Dec 20, 2013

A possible new method for treating pancreatic cancer which enables the body's immune system to attack and kill cancer cells has been developed by researchers.

Fasting time for tumour cells

Mar 15, 2013

(Medical Xpress)—Tumours need a steady supply of sufficient nutrients to be able to grow. In order to secure the nutrient availability, they secrete messenger compounds to stimulate neighbouring blood vessels ...

Recommended for you

Blood biomarker may detect lung cancer

17 hours ago

A new study shows that patients with stage I to stage III non-small cell lung cancer have different metabolite profiles in their blood than those of patients who are at risk but do not have lung cancer. The study abstract ...

ACG: Recent increase in incidence of young-onset CRC

Oct 20, 2014

(HealthDay)—The incidence of young-onset colorectal cancer (CRC) is increasing, and the disease is more aggressive pathologically. These findings are being presented at the annual meeting of the American ...

User comments