Compound shows promise against treatment-resistant cancer cells in lab tests

In collaboration with Adfero

A new compound identified by UK scientists may help to destroy stubborn cancer cells that are resistant to chemotherapy drugs.

Early laboratory tests suggest the compound, ABT-737, could be used to trigger the death of cancer cells in so-called 'hypoxic' regions of solid tumours, where the cells have low concentrations of oxygen.

Cancer cells in these oxygen-starved regions of tumours tend to be resistant to chemotherapy drugs and are therefore hard to treat.

As a result, scientists are keen to discover treatments that are effective in conditions with limited oxygen.

A study by Cancer Research UK scientists at Manchester University has revealed that the addition of the compound ABT-737 to oxygen-deficient samples of human cancer cells - including bowel and small cell lung cancer cells - encourages a natural process of cell death called apoptosis.

It appears to do so by blocking the activity of certain Bcl-2 family proteins, which prevent this process of cell death and are commonly elevated in human cancers.

The researchers then implanted chemotherapy-resistant human cancer cells into mice and found that treatment with ABT-737 caused many of these stubborn cancer cells to die.

The compound was also effective when administered alongside conventional chemotherapy drugs in mice.

This means that, if further tests on animals and clinical trials in humans prove successful, compounds that act in the same way as ABT-737 could provide a useful addition to chemotherapy in patients with solid tumours.

Writing in the Journal of Clinical Investigation, the study authors concluded: "Of potential clinical benefit is the synergy between conventional cytotoxic agents and ABT-737 in hypoxia.

"These data are promising for the treatment of solid tumours, where current therapies reduce or stabilise tumour volume, but where hypoxic tumour cells survive therapy and are the likely cause of tumour repopulation in relapsing cancer patients."

The research team is now carrying out further studies to see whether it may be possible to enhance the compound's effectiveness by adding vascular-targeted drugs.

In addition, a similar compound, ABT-263, is currently in early clinical trials involving patients with solid tumours, including small cell lung cancer.

Oliver Childs, senior science information officer at Cancer Research UK, said: "This work by our scientists shows that these potential cancer drugs can eradicate particularly stubborn tumour cells that are resistant to conventional treatment.

"The next step is to see whether these early lab experiments can be applied to help people with hard-to-treat cancers."